Details of the Researcher

PHOTO

Ko Sato
Section
Graduate School of Medicine
Job title
Assistant Professor
Degree
e-Rad No.
20832124

Research History 6

  • 2023/04 - Present
    東北大学大学院医学系研究科 感染病態学分野

  • 2023/02 - 2026/01
    東北大学プロミナントリサーチフェロー

  • 2021/04 - 2023/03
    東北大学大学院医学系研究科 感染分子病態解析学分野　助教

  • 2018/10 - 2022/09
    Tohoku University Graduate School of Medicine　Department of Intelligent Network for Infection Control　Assistant Professor

  • 2019/07 - 2022/03
    仙台医療センター　臨床研究部ウイルスセンター　客員研究員

  • 2014/04 - 2018/09
    仙台医療センター　臨床研究部ウイルスセンター　臨床検査技師

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Education 3

  • 東北大学大学院　医学系研究科　後期博士課程

    2014/04 - 2018/03

  • 東北大学大学院　医学系研究科　前期博士課程

    2012/04 - 2014/03

  • Tohoku University　Faculty of Medicine　School of Health Sciences, School of Medicine

    2008/04 - 2012/03

Professional Memberships 7

  • JAPANESE ASSOCIATION OF MEDICAL TECHNOLOGISTS

  • THE JAPANESE ASSOCIATION FOR INFECTIOUS DISEASES

  • THE JAPANESE SOCIETY FOR MEDICAL MYCOLOGY

  • JAPANESE SOCIETY FOR BACTERIOLOGY

  • THE JAPANESE SOCIETY FOR VIROLOGY

  • THE JAPANESE SOCIETY FOR IMMUNOLOGY

  • 日本生体防御学会

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Research Interests 3

  • クリプトコックス症

  • ウイルス学

  • 感染免疫

Research Areas 3

  • Life sciences / Virology /

  • Life sciences / Bacteriology /

  • Life sciences / Infectious disease /

Awards 8

  1. 最優秀論文賞

    2022/03　仙台医療センター

  2. 奨励賞

    2021/09　日本生体防御学会

  3. 令和元年度 臨床研究部助成研究報告会 最優秀ポスター賞

    2020/02　仙台医療センター

  4. 第93回日本感染症学会総会・学術講演会 優秀演題賞

    2019/04

  5. 平成29年度仙台医療センター優秀論文賞

    2018/03

  6. 優秀演題賞

    2017/07　第53回宮城県公衆衛生学会学術総会

  7. 平成28年度仙台医療センター優秀論文賞

    2017/03

  8. 若手奨励賞

    2016/06　第57回日本臨床ウイルス学会

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Papers 54

  1. Decreased levels of reduced glutathione impair Th1 immune responses and exacerbate Cryptococcus neoformans infection in diabetic mice. International-journal Peer-reviewed

    Ko Sato, Naoki Kanbayashi, Michiko Yoshida, Emi Kanno, Hiromasa Tanno, Yuki Sato, Keiko Ishii, Tetsuji Aoyagi, Kazuyoshi Kawakami

    Microbial pathogenesis　108741-108741　2026/07/31

    DOI： 10.1016/j.micpath.2026.108741 　

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    Patients with diabetes mellitus (DM) exhibit increased susceptibility to various infectious diseases, and DM represents a critical underlying risk factor for cryptococcosis. However, how diabetic metabolic dysregulation specifically affects host immune responses against Cryptococcus neoformans remains poorly understood. In this study, we investigated anti-cryptococcal immune responses using a streptozotocin (STZ)-induced DM model established in CnT-II transgenic mice, which harbor abundant Cryptococcus-specific CD4+ T cells. Inducing DM directly in these CnT-II mice enabled direct evaluation of antigen-specific immunity. DM mice, which exhibit decreased systemic reduced glutathione (GSH) under chronic hyperglycemia, showed exacerbated cryptococcal infection, characterized by significantly higher pulmonary fungal burdens, decreased IFN-γ levels, reduced survival rates, and defective granuloma formation. In vitro assays using splenocytes from uninfected DM mice revealed significantly impaired cryptococcal antigen-specific Th1 responses, expanded Treg cells, and increased PD-1 expression on CD4+ T cells compared with controls. Specifically, cross-combination cultures of isolated splenic CD4+ T cells and dendritic cells demonstrated that this Th1 impairment was intrinsic to DM-derived T cells, whereas DM-derived dendritic cells had no effect. Additionally, macrophages cultured under high-glucose conditions showed significantly decreased nitric oxide (NO) production and fungicidal activity. Importantly, exogenous GSH supplementation successfully restored both Th1 differentiation and NO production, whereas Treg cell expansion and defective macrophage fungicidal activity were GSH-independent. Taken together, our findings demonstrate how metabolic redox imbalance compromises coordinated host immunity against C. neoformans, offering potential redox-targeted therapeutic insights for diabetic hosts.

  2. Immunological mechanism behind reactivated cryptococcosis in persistently infected mice following FTY720 treatment. International-journal Peer-reviewed

    Michiko Yoshida, Ko Sato, Nana Nakahata, Hayato Sato, Reina Ohagi, Emi Kanno, Hiromasa Tanno, Keiko Ishii, Tetsuji Aoyagi, Atsuo Kikuchi, Kazuyoshi Kawakami

    Infection and immunity　e0061225　2026/04/30

    DOI： 10.1128/iai.00612-25 　

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    The Cryptococcus neoformans species complex (CNSC), responsible for cryptococcosis, is controlled by Th1-type immunity, in which IFN-γ-activated macrophages form granulomas that contain infection. Nevertheless, CNSC can evade host immunity and, after the primary infection phase, can shift to a latent infection similar to tuberculosis. Reactivation is thought to occur when immune control fails, but the underlying mechanisms remain poorly understood. FTY720, a functional antagonist of sphingosine-1-phosphate receptors, is primarily used in the treatment of multiple sclerosis. However, there have been reports linking its use to instances of cryptococcosis in patients undergoing treatment. To explore this, we established a novel mouse model using CnT-II mice, which express CD4+ T cell receptors specific for chitin deacetylase 2 (Cda2), a major T cell antigen of CNSC. Following infection with encapsulated CNSC, mice developed persistent pulmonary fungal burdens (10²-10³ CFU) accompanied by granulomatous responses, modeling latent infection. Upon FTY720 administration, mice exhibited increased pulmonary fungal burdens, disrupted granuloma integrity, and reduced IFN-γ and IL-12 production. FTY720 also markedly decreased CD4+ effector memory (Tem) and effector T cells (Teff) in the lungs, with a particularly profound loss of IFN-γ-producing Tem cells. These findings indicate that our model successfully recapitulates latent cryptococcal infection and reactivation, and demonstrate that FTY720 promotes relapse by depleting protective IFN-γ-producing CD4+ Tem cells and impairing Th1-mediated immunity. Given the rising use of FTY720, our study highlights its potential risk in patients with subclinical cryptococcosis and underscores the need for preventive strategies to avert disease progression.

  3. Human parainfluenza virus type 3 viruses with the furin-susceptible motif at the cleavage site of the fusion protein arose from original wild strains during their propagation in vitro Peer-reviewed

    Yuka Iino, Ko Sato, Yuki Furuse, Emiko Isogai, Hidekazu Nishimura

    Virology　617　110797-110797　2026/04

    Publisher: Elsevier BV

    DOI： 10.1016/j.virol.2026.110797 　

    ISSN： 0042-6822

  4. A transparent osmotic wound dressing ATKPAD promotes the healing process and regulates hypoxia-dependent inflammatory responses. International-journal Peer-reviewed

    Yuki Sato, Eiki Ito, Hiromasa Tanno, Takashi Kanno, Ryuto Arai, Koji Sato, Ayato Kaneta, Wakana Kamada, Ikue Sone, Ko Sato, Shinyo Ishi, Toshiro Imai, Hiromu Matsunaga, Tetsuji Aoyagi, Yoshimichi Imai, Yoshiyuki Adachi, Emi Kanno

    Scientific reports　2026/03/06

    DOI： 10.1038/s41598-026-41264-1 　

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    The inflammatory response after skin injury initiates wound healing by promoting the release of cytokines and growth factors essential for tissue repair. Modern wound dressings promote healing by maintaining a moist, hypoxic environment. ATKPAD is a novel wound dressing that accelerates healing developed by Okamoto Industries, Inc. Composed of reduced starch syrup and a semi-permeable membrane, it was launched in Japan as a Class III medical device in 2024. Transparent ATKPAD allows wound visibility and absorbs exudate in a molecular-weight-dependent manner, with its semi-permeable membrane retaining larger molecules, like cytokines, while letting small molecules pass through osmotic effects rather than specific binding. However, the detailed molecular and cellular mechanisms of ATKPAD remain unclear. In this study, we examined its effect on full-thickness excisional wound healing. We analyzed the in vitro permeability of cytokines and growth factors and evaluated granulation tissue formation, angiogenesis, neutrophil infiltration, and cytokine and growth factor production in vivo. We observed an increase in cytokines and growth factors alongside accelerated wound healing with ATKPAD. Its application enhanced granulation tissue formation and neutrophil infiltration, accompanied by increased expression of Hif1α. These findings suggest that ATKPAD promotes wound healing by creating a hypoxic microenvironment that enhances early-phase inflammation. (Word count: 200).

  5. High Fat Diet-Induced Obesity Alters Cutaneous Immune Cell Function, and These Changes Persist After Weight Loss. International-journal Peer-reviewed

    Wakana Kamada, Hiromasa Tanno, Rena Takayashiki, Yuki Sato, Shinyo Ishi, Miki Shoji, Ko Sato, Tetsuji Aoyagi, Emi Kanno

    Journal of immunology research　2026　(1)　e3930910　2026

    DOI： 10.1155/jimr/3930910 　

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    Obesity is recognized as a chronic low-grade inflammation that contributes to metabolic disorders. Weight loss (WL) is well known to improve metabolic disorders. However, recent studies have shown that the changes in immune cells associated with obesity exhibit immunological memory even after WL. Obesity impairs skin barrier function and exacerbates inflammatory skin diseases, such as psoriasis. While skin immune cells maintain homeostasis and defense, the impact of obesity on these cells in intact skin is understudied, as research mainly focuses on skin with an inflammatory skin disease model in the context of obesity. The effect of WL on skin immunity is even less clear. Therefore, this study aimed to investigate these discrepancies. Mice were assigned to the lean group (regular diet), the obese group (high-fat diet for 18 weeks), and the WL group (high-fat diet for 9 weeks followed by regular diet for 9 weeks). Following 18 weeks of feeding, mouse skin was excised, and immune cell populations within the skin were analyzed using real-time PCR and flow cytometry. In addition, the effects of WL on psoriasis were examined using an imiquimod-induced psoriasis mouse model. We observed increased expression of RORγt, IL-17A, and CCL20 in intact skin in both the obese and WL groups. In the psoriasis model, disease severity was further exacerbated by WL. Moreover, whereas the Vγ4+Vγ5- γδ T cell population was increased in the lean group, the Vγ4-Vγ5- γδ T cell population remained elevated following WL, similar to levels observed in the obese group. These observations indicated that obesity may imprint a memorized immune response in the skin, which is not abrogated by WL. This study is the first to demonstrate this persistent effect on skin immunity. These findings imply that individuals who have experienced obesity may remain at increased risk for inflammatory skin conditions, even after WL.

  6. NKT cell–dependent PspA-specific IgA production caused by mucosal administration of a novel nanoparticle pneumococcal vaccine Peer-reviewed

    Ayako Nakahira, Hiroki Iwaoka, Ko Sato, Shigenari Ishizuka, Ryuhei Shiroma, Tomomitsu Miyasaka, Emi Kanno, Hiromasa Tanno, Yuki Sato, Yukihiro Akeda, Kazunori Oishi, Tetsuji Aoyagi, Keiko Ishii, Kazuyoshi Kawakami

    Vaccine　68　127911-127911　2025/12

    Publisher: Elsevier BV

    DOI： 10.1016/j.vaccine.2025.127911 　

    ISSN： 0264-410X

  7. Defect of Dectin-1-mediated signaling promotes burn wound healing through attenuated oxidative stress and inflammatory responses Peer-reviewed

    Yuki Sato, Hiromasa Tanno, Toshiro Imai, Mai Konno, Rena Takayashiki, Wakana Kamada, Eiki Ito, Ikue Sone, Shiho Kawamoto, Shinyo Ishi, Ko Sato, Keiko Ishii, Tetsuji Aoyagi, Yoichiro Iwakura, Emi Kanno

    Burns　51　(9)　107703-107703　2025/12

    Publisher: Elsevier BV

    DOI： 10.1016/j.burns.2025.107703 　

    ISSN： 0305-4179

  8. Brain-infiltrating CD4 T cells drive inflammatory microglia proliferation during cryptococcal meningitis in mice. International-journal Peer-reviewed

    Sofia Hain, Man Shun Fu, Lucy Wigg, Lorna George, David Lecky, Alexander J Whitehead, Erin Clipston, Ko Sato, Masahiro Ono, Marcel Wuthrich, Bruce Klein, Kazuyoshi Kawakami, Julie Rayes, David Bending, Rebecca A Drummond

    Nature communications　16　(1)　8995-8995　2025/10/09

    DOI： 10.1038/s41467-025-64034-5 　

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    Cryptococcal meningitis is a fungal infection in patients with compromised CD4 T cell function. CD4 T cells provide killing signals to macrophages, principally IFNγ, to limit intracellular fungal replication. However, CD4 T cells may also drive inflammatory tissue damage. Yet, it is not fully understood how fungal-specific CD4 T cells infiltrate the brain and how they influence functional phenotypes of CNS-resident myeloid cells. In the current work, we develop a mouse model to track fungal-specific CD4 T cells and determine their influence on microglia. We found IFNγ+ fungal-specific CD4 T cells have limited TCR signalling and characterise a population of inflammatory microglia that upregulate MHCII and IFNγ-regulated genes during infection. Inflammatory microglia have poor fungicidal capacity and significantly expand during infection, a process that depends on CD4 T cell infiltration. Taken together, these data identify the early inflammatory consequences of fungal-specific CD4 T cell infiltration and identify proliferating microglia as important drivers of brain inflammation during infection.

  9. Cgm1 is a β-galactoside α-(1→4)-mannosyltransferase involved in the biosynthesis of capsular glucuronoxylomannogalactan in Cryptococcus neoformans International-journal Peer-reviewed

    Chihiro Kadooka, Yutaka Tanaka, Ko Sato, Hayato Sato, Daisuke Hira, Shun Yakabe, Kazuyoshi Kawakami, Takuji Oka

    Journal of Biological Chemistry　301　(10)　110632-110632　2025/08

    Publisher: Elsevier BV

    DOI： 10.1016/j.jbc.2025.110632 　

    ISSN： 0021-9258

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    Capsular polysaccharides are present in the outermost layer of the cell wall of Cryptococcus neoformans. The capsule consists of glucuronoxylomannan and glucuronoxylomannogalactan (GXMGal), both of which are major virulence factors that enable immune evasion. This study aimed to identify a novel glycosyltransferase involved in the biosynthesis of capsular polysaccharides in C. neoformans. While glucuronoxylomannan is the predominant capsule component and plays a broad role in immune evasion, GXMGal, despite its lower abundance, is thought to contribute to pathogenicity through its structurally unique galactomannan side chain. Glycosyltransferases involved in GXMGal biosynthesis have attracted much attention as potential targets for antifungal drug development because of their role in pathogenicity. In this study, we identified a novel β-galactoside α-(1 → 4)-mannosyltransferase, cryptococcal β-galactoside mannosyltransferase 1 (Cgm1) (glucan organizing enzyme 1 [Goe1]), which is involved in the biosynthesis of the galactomannan side chain of GXMGal. The GXMGal galactomannan side chain was almost completely lost in the cgm1 (goe1) disruptant, indicating that Cgm1 (Goe1) is the α-(1 → 4)-mannosyltransferase responsible for its biosynthesis. The cgm1 (goe1) disruptant exhibited temperature sensitivity at 37 °C. In addition, interferon-γ production was significantly increased in mice infected with the cgm1 (goe1) disruptant, demonstrating the importance of the galactomannan side chain of GXMGal in immune evasion.

  10. Batroxobin promotes wound healing after burn injury by enhancing blood flow. International-journal Peer-reviewed

    Toshiro Imai, Yuki Sato, Hiromasa Tanno, Wakana Kamada, Shinyo Ishi, Miki Shoji, Hiromu Matsunaga, Ko Sato, Yoshimichi Imai, Emi Kanno

    Plastic and reconstructive surgery　2025/04/01

    DOI： 10.1097/PRS.0000000000012137 　

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    BACKGROUND: In the process of burn wound healing, promoting healing and suppressing wound progression by enhancing blood flow is considered essential. Various agents that increase blood flow are currently being assessed. Batroxobin (DF-521; Defibrase®) is a denitrogenating agent extracted from Bothrops moojeni, used as a thrombin-like serine protease to improve ischemic conditions. However, it remains unclear how this agent affects the burn wound healing process. In this study, we conducted analyses to define the effects of batroxobin administration on burn wound healing. METHODS: Full-thickness burn wounds were created on the dorsal skin of C57BL/6 mice by applying a 90℃, 5-mm-diameter soldering iron for 10 s. Immediately after wounding, batroxobin (30 batroxobin units/kg/mouse) was administered intraperitoneally daily. As a vehicle control, the same volume of saline was administered. We analyzed wound area, histological findings, blood flow, growth factor and chemokine synthesis, and ischemia-reperfusion related factor expression. RESULTS: We found that the systemic administration of batroxobin prevented burn wound progression, which was accompanied by decreased expression of TNF-α and NOX2 and reduced synthesis of Hif-1α. In addition, this agent promoted wound healing by enhancing blood flow, increasing S100A4-positive fibroblast accumulation, and stimulating the production of growth factors (bFGF, EGF, and PlGF). CONCLUSIONS: These results indicate that the systemic administration of batroxobin prevented burn wound progression and accelerated the healing process by enhancing blood flow. (Word count: 222).

  11. Contribution of CARD9 signaling to wound healing in skin promoted by topical administration of heat-killed Enterococcus faecalis strain KH2 and the involvement of Dectin-2. International-journal Peer-reviewed

    Shiho Kurosaka, Hiromasa Tanno, Minako Hirose, Wakana Kamada, Rena Takayashiki, Ikue Sone, Yuki Sato, Takumi Watanabe, Shinyo Ishi, Miki Shoji, Yoshimichi Imai, Ko Sato, Keiko Ishii, Hiromitsu Hara, Sho Yamasaki, Shinobu Saijo, Yoichiro Iwakura, Kazuyoshi Kawakami, Emi Kanno

    Frontiers in immunology　16　1550934-1550934　2025

    DOI： 10.3389/fimmu.2025.1550934 　

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    INTRODUCTION: Lactic acid bacteria (LAB) are well known for their beneficial effects on the regulation of immune responses and host protection against microbial infections. We previously reported that heat-killed Enterococcus faecalis strain KH2 (heat-killed KH2), a species of LAB, enhances inflammatory responses at wound sites and accelerates the skin wound healing process. In this study, we aimed to clarify the pathway underlying the wound-healing effects of heat-killed KH2. We focused on CARD9, a common adaptor molecule for C-type lectin receptors and Dectin-2, the upstream receptor for this adaptor molecule. METHODS: Four full-thickness dermal wounds were created on the backs of wild-type (WT) mice, CARD9 KO mice, and Dectin-2 KO mice, and the effects of heat-killed KH2 administration were examined. We analyzed the percent wound closure, re-epithelialization, granulation tissue formation, and the production of inflammatory cytokines and chemokines. RESULTS: Heat-killed KH2 administration enhanced wound closure, granulation tissue formation, and re-epithelialization in WT mice. However, these effects were absent in heat-killed KH2-treated CARD9 KO mice. Similar results were observed in the migration of neutrophils and the production of TNF-α, IL-6, KC, and MIP-2 in heat-killed KH2-treated CARD9 KO mice. Furthermore, heat-killed KH-2 induced activation of reporter cells expressing Dectin-2. Finally, heat-killed KH-2 treatment in Dectin-2 KO mice did not promote skin wound healing. CONCLUSION: These results suggest that recognition of heat-killed KH2 by Dectin-2 may activate CARD9-mediated signaling, which may contribute to the promotion of skin wound healing through KH2 treatment.

  12. Innate phase production of IFN-γ by memory and effector T cells expressing early activation marker CD69 during infection with Cryptococcus deneoformans in the lungs. International-journal

    Anna Miyahara, Aya Umeki, Ko Sato, Toshiki Nomura, Hideki Yamamoto, Tomomitsu Miyasaka, Daiki Tanno, Ikumi Matsumoto, Tong Zong, Takafumi Kagesawa, Akiho Oniyama, Kotone Kawamura, Xiaoliang Yuan, Rin Yokoyama, Yuki Kitai, Emi Kanno, Hiromasa Tanno, Hiromitsu Hara, Sho Yamasaki, Shinobu Saijo, Yoichiro Iwakura, Keiko Ishii, Kazuyoshi Kawakami

    Infection and immunity　e0002424　2024/05/03

    DOI： 10.1128/iai.00024-24 　

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    Cryptococcus deneoformans is a yeast-type fungus that causes fatal meningoencephalitis in immunocompromised patients and evades phagocytic cell elimination through an escape mechanism. Memory T (Tm) cells play a central role in preventing the reactivation of this fungal pathogen. Among these cells, tissue-resident memory T (TRM) cells quickly respond to locally invaded pathogens. This study analyzes the kinetics of effector T (Teff) cells and Tm cells in the lungs after cryptococcal infection. Emphasis is placed on the kinetics and cytokine expression of TRM cells in the early phase of infection. CD4+ Tm cells exhibited a rapid increase by day 3, peaked at day 7, and then either maintained their levels or exhibited a slight decrease until day 56. In contrast, CD8+ Tm cells reached their peak on day 3 and thereafter decreased up to day 56 post-infection. These Tm cells were predominantly composed of CD69+ TRM cells and CD69+ CD103+ TRM cells. Disruption of the CARD9 gene resulted in reduced accumulation of these TRM cells and diminished interferon (IFN) -γ expression in TRM cells. TRM cells were derived from T cells with T cell receptors non-specific to ovalbumin in OT-II mice during cryptococcal infection. In addition, TRM cells exhibited varied behavior in different tissues. These results underscore the importance of T cells, which produce IFN-γ in the lungs during the early stage of infection, in providing early protection against cryptococcal infection through CARD9 signaling.

  13. CARD9-mediated macrophage responses and collagen fiber capsule formation caused by textured-type breast implants. International-journal Peer-reviewed

    Miki Shoji, Emi Kanno, Hiromasa Tanno, Kenji Yamaguchi, Sinyo Ishi, Naoyuki Takagi, Shiho Kurosaka, Ko Sato, Momoko Niiyama, Akihiko Ito, Keiko Ishii, Yoshimichi Imai, Kazuyoshi Kawakami, Masahiro Tachi

    Plastic and reconstructive surgery　2023/10/17

    DOI： 10.1097/PRS.0000000000011152 　

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    BACKGROUND: An increasing number of women are undergoing breast implantation for cosmetic purposes and for reconstructive purposes after breast excision. The surface morphology of the breast implant is one of the key factors associated with the induction of capsule contraction. The effect of surface morphology on the inflammatory response following implant insertion remains unclear, however. This study conducted comparative analyses to determine the effect of the textured and smooth surface morphology of silicone sheets. METHODS: Each type of silicone sheet was inserted into the subcutaneous pocket below the panniculus carnosus in C57BL/6 mice and mice with genetic disruption of CARD9, Dectin-1, Dectin-2, or Mincle. We also analyzed the collagen fiber capsule thickness, histological findings, and macrophage inflammatory response, including TGF-β synthesis. RESULTS: We found that textured surface morphology contributed to the formation of collagen fiber capsules and the accumulation of fibroblasts and myofibroblasts, and was accompanied by the accumulation of TGF-β-expressing macrophages and foreign-body giant cells. CARD9 deficiency attenuated collagen fiber capsule formation, macrophage responses, and TGF-β synthesis, although the responsible C-type lectin receptors (CLRs) remain to be clarified. CONCLUSIONS: These results suggest that CARD9 may have a strong impact on silicone sheet insertion through the regulation of macrophage responses.

  14. Cutaneous wound healing promoted by topical administration of heat-killed Lactobacillus plantarum KB131 and possible contribution of CARD9-mediated signaling. International-journal Peer-reviewed

    Shinyo Ishi, Emi Kanno, Hiromasa Tanno, Shiho Kurosaka, Miki Shoji, Toshiro Imai, Kenji Yamaguchi, Kanna Kotsugai, Momoko Niiyama, Haruko Kurachi, Fuko Makabe, Takumi Watanabe, Ko Sato, Keiko Ishii, Hiromitsu Hara, Yoshimichi Imai, Kazuyoshi Kawakami

    Scientific reports　13　(1)　15917-15917　2023/09/23

    DOI： 10.1038/s41598-023-42919-z 　

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    Optimal conditions for wound healing require a smooth transition from the early stage of inflammation to proliferation, and during this time alternatively activated (M2) macrophages play a central role. Recently, heat-killed lactic acid bacteria (LAB), such as Lactobacillus plantarum (L. plantarum) have been reported as possible modulators affecting the immune responses in wound healing. However, how signaling molecules regulate this process after the administration of heat-killed LAB remains unclear. In this study, we examined the effect of heat-killed L. plantarum KB131 (KB131) administration on wound healing and the contribution of CARD9, which is an essential signaling adaptor molecule for NF-kB activation upon triggering through C-type lectin receptors, in the effects of this bacterium. We analyzed wound closure, histological findings, and inflammatory responses. We found that administration of KB131 accelerated wound closure, re-epithelialization, granulation area, CD31-positive vessels, and α-SMA-positive myofibroblast accumulated area, as well as the local infiltration of leukocytes. In particular, M2 macrophages were increased, in parallel with CCL5 synthesis. The acceleration of wound healing responses by KB131 was canceled in CARD9-knockout mice. These results indicate that the topical administration of KB131 accelerates wound healing, accompanying increased M2 macrophages, which suggests that CARD9 may be involved in these responses.

  15. PAMPs and host immune response in cryptococcal infection. Invited Peer-reviewed

    Sato K, Kawakami K

    Medical mycology journal　63　(4)　133-138　2022/11

  16. Practical Validation of United States Centers for Disease Control and Prevention Assays for the Detection of Human Respiratory Syncytial Virus in Pediatric Inpatients in Japan International-journal Peer-reviewed

    Reiko Suwa, Yohei Kume, Miyuki Kawase, Mina Chishiki, Takashi Ono, Sakurako Norito, Ko Sato, Michiko Okamoto, Satoru Kumaki, Yukio Nagai, Mitsuaki Hosoya, Makoto Takeda, Hidekazu Nishimura, Koichi Hashimoto, Kazuya Shirato

    Pathogens　11　(7)　754-754　2022/07/01

    Publisher: MDPI AG

    DOI： 10.3390/pathogens11070754 　

    eISSN： 2076-0817

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    The World Health Organization initiated a global surveillance system for respiratory syncytial virus (RSV) in 2015, and the pilot surveillance is ongoing. The real-time RT-PCR RSV assays (Pan-RSV and duplex assays) developed by the United States Centers for Disease Control and Prevention are applied as the standard assays. To introduce these as standard assays in Japan, their practicality was evaluated using 2261 specimens obtained from pediatric inpatients in Japan, which were collected from 2018 to 2021. Although the Pan-RSV and duplex assays had similar analytical sensitivities, they yielded 630 (27.9%) and 786 (34.8%) RSV-positive specimens, respectively (p < 0.001). Although sequencing analysis showed mismatches in the reverse primer used in the Pan-RSV assay, these mismatches did not affect its analytical sensitivity. The analysis of read numbers of RSV isolates from air–liquid interface culture of human bronchial/tracheal epithelial cells showed that the duplex assay had a greater number of reads than did the Pan-RSV assay. Therefore, the duplex assay has superior detection performance compared with the Pan-RSV assay, but the two assays have similar analytical sensitivities.

  17. Suitability of NIID-MDCK cells as a substrate for cell-based influenza vaccine development from the perspective of adventitious virus susceptibility. International-journal Peer-reviewed

    Itsuki Hamamoto, Hitoshi Takahashi, Noriko Shimazaki, Kazuya Nakamura, Katsumi Mizuta, Ko Sato, Hidekazu Nishimura, Norio Yamamoto, Hideki Hasegawa, Takato Odagiri, Masato Tashiro, Eri Nobusawa

    Microbiology and immunology　66　(7)　361-370　2022/05/11

    DOI： 10.1111/1348-0421.12985 　

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    The practical use of cell-based seasonal influenza vaccines is currently being considered in Japan. From the perspective of adventitious virus contamination, we assessed the suitability of NIID-MDCK cells (NIID-MDCK-Cs) as a safe substrate for the isolation of influenza viruses from clinical specimens. We first established a sensitive multiplex real-time PCR system to screen for 27 respiratory viruses and used it on 34 virus samples that were isolated by passaging influenza-positive clinical specimens in NIID-MDCK-Cs. Incidentally, the limit of detection of the system was 100 or fewer genome copies per reaction. In addition to influenza viruses, human enterovirus 68 (HEV-D68) genomes were detected in two samples after two or three passages in NIID-MDCK-Cs. To further investigate the susceptibility of NIID-MDCK-Cs to adventitious viruses, eight common respiratory viruses were subjected to passages in NIID-MDCK-Cs. The genome copy numbers of seven viruses other than parainfluenza 3 decreased below the limit of detection (LOD) by passage 4. By passaging in NIID-MDCK-Cs, the genome numbers of the input HEV-D68, 1 x 108 copies, declined to 102 at passage 3 and to under the LOD at passage 4, whereas those of the other six viruses were under the LOD by passage 3. These results implied that during the process of isolating influenza viruses with NIID-MDCK-Cs, contaminating viruses other than parainfluenza 3 can be efficiently removed by passages in NIID-MDCK-Cs. NIID-MDCK-Cs could be a safe substrate for isolating influenza viruses that can be used to develop cell-based influenza vaccine candidate viruses. This article is protected by copyright. All rights reserved.

  18. Variation in Thermal Stability among Respiratory Syncytial Virus Clinical Isolates under Non-Freezing Conditions International-journal Peer-reviewed

    Yuki Kitai, Ko Sato, Kazuya Shirato, Suguru Ohmiya, Oshi Watanabe, Tomoko Kisu, Reiko Ota, Makoto Takeda, Kazuyoshi Kawakami, Hidekazu Nishimura

    Viruses　14　(4)　679-679　2022/03/25

    Publisher: MDPI AG

    DOI： 10.3390/v14040679 　

    eISSN： 1999-4915

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    Virus isolates are not only useful for diagnosing infections, e.g., respiratory syncytial virus (RSV), but can also facilitate many aspects of practical viral studies such as analyses of antigenicity and the action mechanisms of antivirals, among others. We have been isolating RSV from clinical specimens from patients with respiratory symptoms every year since our first isolation of RSV in 1964, and isolation rates have varied considerably over the years. As collected clinical specimens are conventionally stored in a refrigerator from collection to inoculation into cells, we hypothesized that certain storage conditions or associated factors might account for these differences. Hence, we evaluated the thermal stability of a total of 64 viruses isolated from 1998 to 2018 upon storage at 4 °C and 20 °C for a defined duration. Interestingly, and contrary to our current understanding, 22 strains (34%) showed a greater loss of viability upon short-term storage at 4 °C than at 20 °C. Thirty-seven strains (57%) showed an almost equal loss, and only five strains (8%) were more stable at 4 °C than at 20 °C. This finding warrants reconsideration of the temperature for the temporary storage of clinical samples for RSV isolation.

  19. Topical administration of heat-killed enterococcus faecalis strain kh2 promotes re-epithelialization and granulation tissue formation during skin wound-healing Peer-reviewed

    Hiromasa Tanno, Emi Kanno, Shiho Kurosaka, Yukari Oikawa, Takumi Watanabe, Ko Sato, Jun Kasamatsu, Tomomitsu Miyasaka, Shinyo Ishi, Miki Shoji, Naoyuki Takagi, Yoshimichi Imai, Keiko Ishii, Masahiro Tachi, Kazuyoshi Kawakami

    Biomedicines　9　(11)　2021/11

    DOI： 10.3390/biomedicines9111520 　

    eISSN： 2227-9059

  20. Deficiency of lung-specific claudin-18 leads to aggravated infection with Cryptococcus deneoformans through dysregulation of the microenvironment in lungs. International-journal Peer-reviewed

    Ko Sato, Ikumi Matsumoto, Koya Suzuki, Atsushi Tamura, Aki Shiraishi, Hiroshi Kiyonari, Jun Kasamatsu, Hideki Yamamoto, Tomomitsu Miyasaka, Daiki Tanno, Anna Miyahara, Tong Zong, Takafumi Kagesawa, Akiho Oniyama, Kotone Kawamura, Yuki Kitai, Aya Umeki, Emi Kanno, Hiromasa Tanno, Keiko Ishii, Sachiko Tsukita, Kazuyoshi Kawakami

    Scientific reports　11　(1)　21110-21110　2021/10/26

    DOI： 10.1038/s41598-021-00708-6 　

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    Cryptococcus deneoformans is an opportunistic fungal pathogen that infects the lungs via airborne transmission and frequently causes fatal meningoencephalitis. Claudins (Cldns), a family of proteins with 27 members found in mammals, form the tight junctions within epithelial cell sheets. Cldn-4 and 18 are highly expressed in airway tissues, yet the roles of these claudins in respiratory infections have not been clarified. In the present study, we analyzed the roles of Cldn-4 and lung-specific Cldn-18 (luCldn-18) in host defense against C. deneoformans infection. luCldn-18-deficient mice exhibited increased susceptibility to pulmonary infection, while Cldn-4-deficient mice had normal fungal clearance. In luCldn-18-deficient mice, production of cytokines including IFN-γ was significantly decreased compared to wild-type mice, although infiltration of inflammatory cells including CD4+ T cells into the alveolar space was significantly increased. In addition, luCldn-18 deficiency led to high K+ ion concentrations in bronchoalveolar lavage fluids and also to alveolus acidification. The fungal replication was significantly enhanced both in acidic culture conditions and in the alveolar spaces of luCldn-18-deficient mice, compared with physiological pH conditions and those of wild-type mice, respectively. These results suggest that luCldn-18 may affect the clinical course of cryptococcal infection indirectly through dysregulation of the alveolar space microenvironment.

  21. Contribution of invariant natural killer t cells to the clearance of pseudomonas aeruginosa from skin wounds Peer-reviewed

    Hiromasa Tanno, Emi Kanno, Suzuna Sato, Yu Asao, Mizuki Shimono, Shiho Kurosaka, Yukari Oikawa, Shinyo Ishi, Miki Shoji, Ko Sato, Jun Kasamatsu, Tomomitsu Miyasaka, Hideki Yamamoto, Keiko Ishii, Yoshimichi Imai, Masahiro Tachi, Kazuyoshi Kawakami

    International Journal of Molecular Sciences　22　(8)　2021/04

    DOI： 10.3390/ijms22083931 　

    ISSN： 1661-6596

    eISSN： 1422-0067

  22. TMPRSS2 activates hemagglutinin-esterase glycoprotein of influenza C virus. International-journal Peer-reviewed

    Ko Sato, Hideki Hayashi, Yoshitaka Shimotai, Mutsuo Yamaya, Seiji Hongo, Kazuyoshi Kawakami, Yoko Matsuzaki, Hidekazu Nishimura

    Journal of virology　JVI0129621　2021

    DOI： 10.1128/JVI.01296-21 　

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    Influenza C virus (ICV) has only one kind of spike protein, the hemagglutinin-esterase (HE) glycoprotein. HE functions similarly to hemagglutinin (HA) and neuraminidase of the influenza A and B viruses (IAV/IBV). It has a monobasic site, which is cleaved by some host enzyme(s). The cleavage is essential to activating the virus, but the enzyme(s) in the respiratory tract has not been identified. This study investigated whether the host serine proteases, transmembrane protease serine S1, members 2 (TMPRSS2), and human airway trypsin-like protease (HAT), which reportedly cleave HA of IAV/IBV, are involved in HE cleavage. We established TMPRSS2- and HAT-expressing MDCK (MDCK-TMPRSS2, MDCK-HAT) cells. ICV showed multicycle replication with HE cleavage without trypsin in MDCK-TMPRSS2 cells as well as IAV did. The HE cleavage and multicycle replication did not appear in MDCK-HAT cells infected with ICV without trypsin, while HA cleavage and multi-step growth of IAV appeared in the cells. Amino acid sequences of the HE cleavage site in 352 ICV strains were completely preserved. Camostat and nafamostat suppressed the growth of ICV and IAV in human nasal surface epithelial (HNE) cells. Therefore, this study revealed that, at least, TMPRSS2 is involved in HE cleavage and suggested that nafamostat could be a candidate for therapeutic drugs of ICV infection. Importance Influenza C virus (ICV) is a pathogen that causes acute respiratory illness, mostly in children, but there are no anti-ICV drugs. ICV has only one kind of spike protein, the hemagglutinin-esterase (HE) glycoprotein on the virion surface, that possesses receptor binding, receptor destroying, and membrane fusion activities. The HE cleavage is essential for the virus to be activated, but the enzyme(s) in the respiratory tract has not been identified. This study revealed that transmembrane protease serine S1, members 2 (TMPRSS2), and not human airway trypsin-like protease (HAT), is involved in HE cleavage. This is a novel study on the host enzymes involved in HE cleavage, and the result suggests that the host enzymes, such as TMPRSS2, may be a target for therapeutic drugs of the ICV infection.

  23. Role of Dectin-2 in the phagocytosis of Cryptococcus neoformans by dendritic cells. Peer-reviewed

    Yuki Kitai, Ko Sato, Daiki Tanno, Xiaoliang Yuan, Aya Umeki, Jun Kasamatsu, Emi Kanno, Hiromasa Tanno, Hiromitsu Hara, Sho Yamasaki, Shinobu Saijo, Yoichiro Iwakura, Keiko Ishii, Kazuyoshi Kawakamia

    Infection and Immunity　89　(10)　2021

    DOI： 10.1128/IAI.00330-21 　

    ISSN： 0019-9567

    eISSN： 1098-5522

  24. Dectin-2-mediated initiation of immune responses caused by influenza virus hemagglutinin. Peer-reviewed

    Hideki Yamamoto, Chikako Tomiyama, Ko Sato, Jun Kasamatsu, Kazuki Takano, Aya Umeki, Nana Nakahata, Tomomitsu Miyasaka, Emi Kanno, Hiromasa Tanno, Sho Yamasaki, Shinobu Saijo, Yoichiro Iwakura, Keiko Ishii, Kazuyoshi Kawakami

    Biomedical research (Tokyo, Japan)　42　(2)　53-66　2021

    DOI： 10.2220/biomedres.42.53 　

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    Antigen-presenting cells express pattern recognition receptors (PRRs), which sense pathogen-associated molecular patterns from microorganisms and lead to the induction of inflammatory responses. C-type lectin receptors (CLRs), the representative PRRs, bind to microbial polysaccharides, among which Dectin-2 and Mincle recognize mannose-containing polysaccharides. Because influenza virus (IFV) hemagglutinin (HA) is rich in mannose polysaccharides, Dectin-2 or Mincle may contribute to the recognition of HA. In this study, we addressed the possible involvement of Dectin-2 and Mincle in the viral recognition and the initiation of cytokine production. Interleukin (IL)-12p40 and IL-6 production by bone marrow-derived dendritic cells (BM-DCs) upon stimulation with HA was significantly reduced in Dectin-2 knockout (KO) mice compared to wild-type (WT) mice whereas there was no difference between WT mice and Mincle KO mice. BM-DCs that were treated with Syk inhibitor resulted in a significant reduction of cytokine production upon stimulation with HA. The treatment of BM-DCs with methyl-α-D-mannopyranoside (ManP) also led to a significant reduction in cytokine production by BM-DCs that were stimulated with HA, except for the A/H1N1pdm09 subtype. IL-12p40 and IL-6 synthesis by BM-DCs was completely diminished upon stimulation with HA treated with concanavalin A (ConA)-bound sepharose beads. Finally, GFP expression was detected in reporter cells that were transfected with the Dectin-2 gene, but not with the Mincle gene, when stimulated with HA derived from the A/H3N2 subtype. These data suggested that Dectin-2 may be a key molecule as the sensor for IFV to initiate the immune response and regulate the pathogenesis of IFV infection.

  25. Distinct Roles for Dectin-1 and Dectin-2 in Skin Wound Healing and Neutrophilic Inflammatory Responses. International-journal Peer-reviewed

    Kenji Yamaguchi, Emi Kanno, Hiromasa Tanno, Ayako Sasaki, Yuki Kitai, Takayuki Miura, Naoyuki Takagi, Miki Shoji, Jun Kasamatsu, Ko Sato, Yuka Sato, Momoko Niiyama, Yuka Goto, Keiko Ishii, Yoshimichi Imai, Shinobu Saijo, Yoichiro Iwakura, Masahiro Tachi, Kazuyoshi Kawakami

    The Journal of investigative dermatology　141　(1)　164-176　2021/01

    DOI： 10.1016/j.jid.2020.04.030 　

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    C-type lectin receptors recognize microbial polysaccharides. The C-type lectin receptors such as dendritic cell-associated C-type lectin (Dectin)-1 and Dectin-2, which are triggered by β-glucan and α-mannan, respectively, contribute to upregulation of the inflammatory response. Recently, we demonstrated that activation of the Dectin-2 signal delayed wound healing; in previous studies, triggering the Dectin-1 signal promoted this response. However, the precise roles of these C-type lectin receptors in skin wound healing remain unclear. This study was conducted to determine the roles of Dectin-1 and Dectin-2 in skin wound healing, with a particular focus on the kinetics of neutrophilic inflammatory response. Full-thickness wounds were created on the backs of C57BL/6 mice, and the effects of Dectin-1 or Dectin-2 deficiency and those of β-glucan or α-mannan administration were examined. We also analyzed wound closure, histological findings, and neutrophilic inflammatory response, including neutrophil extracellular trap formation at the wound sites. We found that Dectin-1 contributed to the acceleration of wound healing by inducing early-phase neutrophil accumulation, whereas Dectin-2 was involved in prolonged neutrophilic responses and neutrophil extracellular trap formation, leading to delayed wound healing. Dectin-2 deficiency also improved collagen deposition and TGF-β1 expression. These results suggest that Dectin-1 and Dectin-2 have different roles in wound healing through their different effects on the neutrophilic response.

  26. Effect of CARD9 Deficiency on Neutrophil-Mediated Host Defense against Pulmonary Infection with Streptococcus pneumoniae. International-journal Peer-reviewed

    Shigenari Ishizuka, Rin Yokoyama, Ko Sato, Ryuhei Shiroma, Ayako Nakahira, Hideki Yamamoto, Kazuki Takano, Takafumi Kagesawa, Tomomitsu Miyasaka, Jun Kasamatsu, Emi Kanno, Hiromasa Tanno, Keiko Ishii, Kazuyoshi Kawakami

    Infection and immunity　89　(1)　2020/12/15

    DOI： 10.1128/IAI.00305-20 　

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    Streptococcus pneumoniae is a major causative bacterium of community-acquired pneumonia. Dendritic cell-associated C-type lectin-2 (dectin-2), one of the C-type lectin receptors (CLRs), was previously reported to play a pivotal role in host defense against pneumococcal infection through regulating phagocytosis by neutrophils while not being involved in neutrophil accumulation. In the present study, to elucidate the possible contribution of other CLRs to neutrophil accumulation, we examined the role of caspase recruitment domain-containing protein 9 (CARD9), a common adaptor molecule for signal transduction triggered by CLRs, in neutrophilic inflammatory response against pneumococcal infection. Wild-type (WT), CARD9 knockout (KO), and dectin-2 KO mice were infected intratracheally with pneumococcus, and the infected lungs were histopathologically analyzed to assess neutrophil accumulation at 24 h postinfection. Bronchoalveolar lavage fluids (BALFs) were collected at the same time point to count the neutrophils and assess the production of inflammatory cytokines and chemokines. Neutrophil accumulation was significantly decreased in CARD9 KO mice, but not in dectin-2 KO mice. Tumor necrosis factor alpha (TNF-α), keratinocyte-derived chemokine (KC), and macrophage inflammatory protein-2 (MIP-2) production in BALFs were also attenuated in CARD9 KO mice, but not in dectin-2 KO mice. Production of TNF-α and KC by alveolar macrophages stimulated with pneumococcal culture supernatants was significantly attenuated in CARD9 KO mice, but not in dectin-2 KO mice, compared to that in each group's respective control mice. In addition, pneumococcus-infected CARD9 KO mice showed larger bacterial burdens in the lungs than did WT mice. These data indicate that CARD9 is required for neutrophil migration after pneumococcal infection, as well as inflammatory cytokine and chemokine production by alveolar macrophages, and suggest that a CLR distinct from dectin-2 may be involved in this response.

  27. Limited Role of Mincle in the Host Defense against Infection with Cryptococcus deneoformans. International-journal Peer-reviewed

    Yuki Sato, Ko Sato, Hideki Yamamoto, Jun Kasamatsu, Tomomitsu Miyasaka, Daiki Tanno, Anna Miyahara, Takafumi Kagesawa, Akiho Oniyama, Kotone Kawamura, Rin Yokoyama, Yuki Kitai, Aya Umeki, Shigenari Ishizuka, Kazuki Takano, Ryuhei Shiroma, Nana Nakahata, Kaori Kawakami, Emi Kanno, Hiromasa Tanno, Sho Yamasaki, Hiromitsu Hara, Keiko Ishii, Kazuyoshi Kawakami

    Infection and immunity　88　(11)　2020/10/19

    DOI： 10.1128/IAI.00400-20 　

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    Cryptococcus deneoformans is an opportunistic fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired cell-mediated immune responses such as AIDS. Caspase-associated recruitment domain 9 (CARD9) plays a critical role in the host defense against cryptococcal infection, suggesting the involvement of one or more C-type lectin receptors (CLRs). In the present study, we analyzed the role of macrophage-inducible C-type lectin (Mincle), one of the CLRs, in the host defense against C. deneoformans infection. Mincle expression in the lungs of wild-type (WT) mice was increased in the early stage of cryptococcal infection in a CARD9-dependent manner. In Mincle gene-disrupted (Mincle KO) mice, the clearance of this fungus, pathological findings, Th1/Th2 response, and antimicrobial peptide production in the infected lungs were nearly comparable to those in WT mice. However, the production of interleukin-22 (IL-22), tumor necrosis factor alpha (TNF-α), and IL-6 and the expression of AhR were significantly decreased in the lungs of Mincle KO mice compared to those of WT mice. In in vitro experiments, TNF-α production by bone marrow-derived dendritic cells was significantly decreased in Mincle KO mice. In addition, the disrupted lysates of C. deneoformans, but not those of whole yeast cells, activated Mincle-triggered signaling in an assay with a nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing this receptor. These results suggest that Mincle may be involved in the production of Th22-related cytokines at the early stage of cryptococcal infection, although its role may be limited in the host defense against infection with C. deneoformans.

  28. Recent Molecular Evolution of Human Metapneumovirus (HMPV): Subdivision of HMPV A2b Strains. International-journal Peer-reviewed

    Naganori Nao, Miwako Saikusa, Ko Sato, Tsuyoshi Sekizuka, Shuzo Usuku, Nobuko Tanaka, Hidekazu Nishimura, Makoto Takeda

    Microorganisms　8　(9)　1280　2020/08/21

    DOI： 10.3390/microorganisms8091280 　

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    Human metapneumovirus (HMPV) is a major etiological agent of acute respiratory infections in humans. HMPV has been circulating worldwide for more than six decades and is currently divided into five agreed-upon subtypes: A1, A2a, A2b, B1, and B2. Recently, the novel HMPV subtypes A2c, A2b1, and A2b2 have been proposed. However, the phylogenetic and evolutionary relationships between these recently proposed HMPV subtypes are unclear. Here, we report a genome-wide phylogenetic and evolutionary analysis of 161 HMPV strains, including unique HMPV subtype A2b strains with a 180- or 111-nucleotide duplication in the G gene (nt-dup). Our data demonstrate that the HMPV A2b subtype contains two distinct subtypes, A2b1 and A2b2, and that the HMPV subtypes A2c and A2b2 may be different names for the same subtype. HMPV A2b strains with a nt-dup also belong to subtype A2b2. Molecular evolutionary analyses indicate that subtypes A2b1 and A2b2 diverged from subtype A2b around a decade after the subtype A2 was divided into the subtypes A2a and A2b. These data support the A2b1 and A2b2 subtypes proposed in 2012 and are essential for the unified classification of HMPV subtype A2 strains, which is important for future HMPV surveillance and epidemiological studies.

  29. Production of IL-17A at Innate Immune Phase Leads to Decreased Th1 Immune Response and Attenuated Host Defense against Infection with Cryptococcus deneoformans. International-journal Peer-reviewed

    Ko Sato, Hideki Yamamoto, Toshiki Nomura, Jun Kasamatsu, Tomomitsu Miyasaka, Daiki Tanno, Ikumi Matsumoto, Takafumi Kagesawa, Anna Miyahara, Tong Zong, Akiho Oniyama, Kotone Kawamura, Rin Yokoyama, Yuki Kitai, Shigenari Ishizuka, Emi Kanno, Hiromasa Tanno, Hiromi Suda, Masanobu Morita, Masayuki Yamamoto, Yoichiro Iwakura, Keiko Ishii, Kazuyoshi Kawakami

    Journal of immunology (Baltimore, Md. : 1950)　205　(3)　686-698　2020/08/01

    DOI： 10.4049/jimmunol.1901238 　

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    IL-17A is a proinflammatory cytokine produced by many types of innate immune cells and Th17 cells and is involved in the elimination of extracellularly growing microorganisms, yet the role of this cytokine in the host defense against intracellularly growing microorganisms is not well known. Cryptococcus deneoformans is an opportunistic intracellular growth fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired immune responses. In the current study, we analyzed the role of IL-17A in the host defense against C. deneoformans infection. IL-17A was quickly produced by γδT cells at an innate immune phase in infected lungs. In IL-17A gene-disrupted mice, clearance of this fungal pathogen and the host immune response mediated by Th1 cells were significantly accelerated in infected lungs compared with wild-type mice. Similarly, killing of this fungus and production of inducible NO synthase and TNF-α were significantly enhanced in IL-17A gene-disrupted mice. In addition, elimination of this fungal pathogen, Th1 response, and expression of IL-12Rβ2 and IFN-γ in NK and NKT cells were significantly suppressed by treatment with rIL-17A. The production of IL-12p40 and TNF-α from bone marrow-derived dendritic cells stimulated with C. deneoformans was significantly suppressed by rIL-17A. In addition, rIL-17A attenuated Th1 cell differentiation in splenocytes from transgenic mice highly expressing TCR for mannoprotein 98, a cryptococcal Ag, upon stimulation with recombinant mannoprotein 98. These data suggest that IL-17A may be involved in the negative regulation of the local host defense against C. deneoformans infection through suppression of the Th1 response.

  30. Pneumococcal vaccines: Current status and future perspectives

    Ko Sato, Keiko Ishii, Kazuyoshi Kawakami

    Japanese Journal of Chemotherapy　68　(4)　518-531　2020/07/01

    Publisher: Japan Society of Chemotherapy

    ISSN： 1340-7007

  31. 肺炎球菌感染症に対する現行ワクチンの特徴と次世代ワクチンの開発 Invited Peer-reviewed

    佐藤 光, 石井 恵子, 川上 和義

    日本化学療法学会雑誌　68　(4)　518-531　2020/07

    Publisher: (公社)日本化学療法学会

    ISSN： 1340-7007

    eISSN： 1884-5886

  32. インフルエンザウイルス抗原迅速検出キットでA、B両型陽性を示し、種々のウイルス学的解析により偽陽性反応が確認された1例について

    大宮 卓, 佐藤 光, 西村 秀一

    医学検査　69　(3)　463-467　2020/07

    Publisher: (一社)日本臨床衛生検査技師会

    ISSN： 0915-8669

    eISSN： 2188-5346

  33. パラインフルエンザウイルス感染症の小児285例の臨床的特徴と重症化リスク因子の検討 Peer-reviewed

    三浦拓人, 鈴木聡志, 大宮卓, 渡邊王志, 石田智之, 渡邊庸平, 大沼良一, 貴田岡節子, 佐藤光, 西村秀一, 久間木悟

    仙台医療センター医学雑誌　10　42-45　2020/06

  34. Novel Toll-Like Receptor 9 Agonist Derived from Cryptococcus neoformans Attenuates Allergic Inflammation Leading to Asthma Onset in Mice. International-journal Peer-reviewed

    Kaori Dobashi-Okuyama, Kazuyoshi Kawakami, Tomomitsu Miyasaka, Ko Sato, Keiko Ishii, Kaori Kawakami, Chiaki Masuda, Syugo Suzuki, Jun Kasamatsu, Hideki Yamamoto, Daiki Tanno, Emi Kanno, Hiromasa Tanno, Tasuku Kawano, Motoaki Takayanagi, Tomoko Takahashi, Isao Ohno

    International archives of allergy and immunology　181　(9)　651-664　2020

    Publisher: S. Karger AG

    DOI： 10.1159/000508535 　

    ISSN： 1018-2438

    eISSN： 1423-0097

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    INTRODUCTION: The enhanced type 2 helper (Th2) immune response is responsible for the pathogenesis of allergic asthma. To suppress the enhanced Th2 immune response, activation of the Th1 immune response has been an alternative strategy for anti-asthma therapy. In this context, effective Th1-inducing adjuvants that inhibit the development of allergic asthma but do not flare the side effects of the primary agent are required in clinical treatment and preventive medicine. OBJECTIVE: In this study, we aimed to determine the regulation of the Th2 type immune response in asthma by a novel immunostimulatory oligodeoxynucleotide (ODN) derived from Cryptococcus neoformans, termed ODN112, which contains a cytosine-guanine (CG) sequence but not canonical CpG motifs. METHODS: Using an ovalbumin-induced asthma mouse model, we assessed the effect of ODN112 on prototypical asthma-related features in the lung and on the Th1/Th2 profile in the lymph nodes and lung of mice treated with ODN112 during sensitization. RESULTS AND CONCLUSION: ODN112 treatment attenuated asthma features in mice. In the bronchial lymph nodes of the lungs and in the spleen, ODN112 increased interferon-γ production and attenuated Th2 recall responses. In dendritic cells (DCs) after allergen sensitization, ODN112 enhanced cluster of differentiation (CD) 40 and CD80 expression but did not alter CD86 expression. Interleukin-12p40 production from DCs was also increased in a Th2-polarizing condition. Our results suggest that ODN112 is a potential Th1-inducing adjuvant during Th2 cell differentiation in the sensitization phase.

  35. Low response in eliciting neuraminidase inhibition activity of sera among recipients of a split, monovalent pandemic influenza vaccine during the 2009 pandemic. International-journal Peer-reviewed

    Hiroko Ito, Hidekazu Nishimura, Tomoko Kisu, Haruhisa Hagiwara, Oshi Watanabe, Francois Marie Ngako Kadji, Ko Sato, Suguru Omiya, Emi Takashita, Eri Nobusawa

    PloS one　15　(5)　e0233001　2020

    DOI： 10.1371/journal.pone.0233001 　

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    Antibodies against influenza virus neuraminidase (NA) protein prevent releasing of the virus from host cells and spreading of infection foci and are considered the 'second line of defence' against influenza. Haemagglutinin inhibition antibody-low responders (HI-LRs) are present among influenza split vaccine recipients. The NA inhibition (NAI) antibody response in vaccinees is worth exploring, especially those in the HI-LRs population. We collected pre- and post-vaccination sera from 61 recipients of an inactivated, monovalent, split vaccine against A/H1N1pdm09 and acute and convalescent sera from 49 unvaccinated patients naturally infected with the A/H1N1pdm09 virus during the 2009 influenza pandemic. All samples were subjected to haemagglutinin inhibition (HI), NAI and neutralisation assays. Most paired sera from naturally infected patients exhibited marked elevation in the NAI activity, and seroconversion rates (SCR) among HI-LRs and HI-responders (HI-Rs) were 60% and 87%, respectively; however, those from vaccinees displayed low increase in the NAI activity, and the SCR among HI-LRs and HI-Rs were 0% and 12%, respectively. In both HI-LRs and HI-Rs, vaccination with the inactivated, monovalent, split vaccine failed to elicit the NAI activity efficiently in the sera of the naive population, compared with the natural infection. Hence, the improvement of influenza vaccines is warranted to elicit not only HI but also NAI antibodies.

  36. Dectin-2-mediated signaling triggered by the cell wall polysaccharides of Cryptococcus neoformans. International-journal Peer-reviewed

    Daiki Tanno, Rin Yokoyama, Kotone Kawamura, Yuki Kitai, Xiaoliang Yuan, Keiko Ishii, Magdia De Jesus, Hideki Yamamoto, Ko Sato, Tomomitsu Miyasaka, Hiroki Shimura, Nobuyuki Shibata, Yoshiyuki Adachi, Naohito Ohno, Sho Yamasaki, Kazuyoshi Kawakami

    Microbiology and immunology　63　(12)　500-512　2019/12

    DOI： 10.1111/1348-0421.12746 　

    ISSN： 0385-5600

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    Cryptococcus neoformans is rich in polysaccharides of the cell wall and capsule. Dectin-2 recognizes high-mannose polysaccharides and plays a central role in the immune response to fungal pathogens. Previously, we demonstrated Dectin-2 was involved in the activation of dendritic cells upon stimulation with C. neoformans, suggesting the existence of a ligand recognized by Dectin-2. In the present study, we examined the cell wall structures of C. neoformans contributing to the Dectin-2-mediated activation of immune cells. In a NFAT-GFP reporter assay of the reported cells expressing Dectin-2, the lysates, but not the whole yeast cells, of an acapsular strain of C. neoformans (Cap67) delivered Dectin-2-mediated signaling. This activity was detected in the supernatant of β-glucanase-treated Cap67 and more strongly in the semi-purified polysaccharides of this supernatant using ConA-affinity chromatography (ConA-bound fraction), in which a large amount of saccharides, but not protein, were detected. Treatment of this supernatant with periodic acid and the addition of excessive mannose, but not glucose or galactose, strongly inhibited this activity. The ConA-bound fraction of the β-glucanase-treated Cap67 supernatant was bound to Dectin-2-Fc fusion protein in a dose-dependent manner and strongly induced the production of interleukin-12p40 and tumour necrosis factor-α by dendritic cells; this was abrogated under the Dectin-2-deficient condition. Finally, 98 kDa mannoprotein (MP98) derived from C. neoformans showed activation of the reporter cells expressing Dectin-2. These results suggested that a ligand with mannose moieties may exist in the cell walls and play a critical role in the activation of dendritic cells during infection with C. neoformans.

  37. Defect of Interferon γ Leads to Impaired Wound Healing through Prolonged Neutrophilic Inflammatory Response and Enhanced MMP-2 Activation. International-journal Peer-reviewed

    Emi Kanno, Hiromasa Tanno, Airi Masaki, Ayako Sasaki, Noriko Sato, Maiko Goto, Mayu Shisai, Kenji Yamaguchi, Naoyuki Takagi, Miki Shoji, Yuki Kitai, Ko Sato, Jun Kasamatsu, Keiko Ishii, Tomomitsu Miyasaka, Kaori Kawakami, Yoshimichi Imai, Yoichiro Iwakura, Ryoko Maruyama, Masahiro Tachi, Kazuyoshi Kawakami

    International journal of molecular sciences　20　(22)　2019/11/12

    DOI： 10.3390/ijms20225657 　

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    Interferon (IFN)-γ is mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. Although IFN-γ is well known regarding its inhibitory effects on collagen synthesis by fibroblasts in vitro, information is limited regarding its role in wound healing in vivo. In the present study, we analyzed how the defect of IFN-γ affects wound healing. Full-thickness wounds were created on the backs of wild type (WT) C57BL/6 and IFN-γ-deficient (KO) mice. We analyzed the percent wound closure, wound breaking strength, accumulation of leukocytes, and expression levels of COL1A1, COL3A1, and matrix metalloproteinases (MMPs). IFN-γKO mice exhibited significant attenuation in wound closure on Day 10 and wound breaking strength on Day 14 after wound creation, characteristics that are associated with prolonged neutrophil accumulation. Expression levels of COL1A1 and COL3A1 mRNA were lower in IFN-γKO than in WT mice, whereas expression levels of MMP-2 (gelatinase) mRNA were significantly greater in IFN-γKO than in WT mice. Moreover, under neutropenic conditions created with anti-Gr-1 monoclonal antibodies, wound closure in IFN-γKO mice was recovered through low MMP-2 expression levels. These results suggest that IFN-γ may be involved in the proliferation and maturation stages of wound healing through the regulation of neutrophilic inflammatory responses.

  38. Fluctuations in antibody titers against enterovirus D68 in pediatric sera collected in a community before, during, and after a possible outbreak. Peer-reviewed

    Kadji FMN, Nishimura H, Okamoto M, Sato K, Ohmiya S, Ito H, Suzuki A, Nagai Y, Oshitani H

    Japanese journal of infectious diseases　73　(1)　55-57　2019/08

    DOI： 10.7883/yoken.JJID.2019.056 　

    ISSN： 1344-6304

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    We previously reported a hospital-based epidemiological study on enterovirus (EV)-D68 infection among children during the autumn of 2015, which indirectly inferred an outbreak in Sendai, Japan. In this study, stocked sera of children (aged 0-6 years; without symptoms of infectious diseases) in the Sendai community collected during 4 periods (1 year before, 6 months before, immediately after, and 1 year after the possible outbreak period) were analyzed using the neutralization antibody titer assay to determine community children's immunity levels against EV-D68 infection. The immunity levels were confirmed to have increased during the possible outbreak period and to have gradually waned over 1 year without another outbreak. These results provide background information supporting the results of our previous hospital-based surveillance study.

  39. Consensus and variations in cell line specificity among human metapneumovirus strains. International-journal Peer-reviewed

    Naganori Nao, Ko Sato, Junya Yamagishi, Maino Tahara, Yuichiro Nakatsu, Fumio Seki, Hiroshi Katoh, Aiko Ohnuma, Yuta Shirogane, Masahiro Hayashi, Tamio Suzuki, Hideaki Kikuta, Hidekazu Nishimura, Makoto Takeda

    PloS one　14　(4)　e0215822　2019

    DOI： 10.1371/journal.pone.0215822 　

    More details Close

    Human metapneumovirus (HMPV) has been a notable etiological agent of acute respiratory infection in humans, but it was not discovered until 2001, because HMPV replicates only in a limited number of cell lines and the cytopathic effect (CPE) is often mild. To promote the study of HMPV, several groups have generated green fluorescent protein (GFP)-expressing recombinant HMPV strains (HMPVGFP). However, the growing evidence has complicated the understanding of cell line specificity of HMPV, because it seems to vary notably among HMPV strains. In addition, unique A2b clade HMPV strains with a 180-nucleotide duplication in the G gene (HMPV A2b180nt-dup strains) have recently been detected. In this study, we re-evaluated and compared the cell line specificity of clinical isolates of HMPV strains, including the novel HMPV A2b180nt-dup strains, and six recombinant HMPVGFP strains, including the newly generated recombinant HMPV A2b180nt-dup strain, MG0256-EGFP. Our data demonstrate that VeroE6 and LLC-MK2 cells generally showed the highest infectivity with any clinical isolates and recombinant HMPVGFP strains. Other human-derived cell lines (BEAS-2B, A549, HEK293, MNT-1, and HeLa cells) showed certain levels of infectivity with HMPV, but these were significantly lower than those of VeroE6 and LLC-MK2 cells. Also, the infectivity in these suboptimal cell lines varied greatly among HMPV strains. The variations were not directly related to HMPV genotypes, cell lines used for isolation and propagation, specific genome mutations, or nucleotide duplications in the G gene. Thus, these variations in suboptimal cell lines are likely intrinsic to particular HMPV strains.

  40. 【インフルエンザワクチン:再考と展望】経鼻インフルエンザ生ワクチンの動向 Invited Peer-reviewed

    佐藤 光, 西村 秀一

    外来小児科　21　(3)　414-420　2018/11

    Publisher: (一社)日本外来小児科学会

    ISSN： 1345-8043

  41. Case study-based time-course analysis of symptoms of respiratory syncytial virus infections followed by acute sinusitis in otherwise-healthy adults Peer-reviewed

    Hidekazu Nishimura, Ko Sato, Francois Marie Ngako Kadji, Suguru Ohmiya, Hiroko Ito, Toru Kubo, Sho Hashimoto

    Journal of Thoracic Disease　10　(5)　E322-E327　2018/05/01

    DOI： 10.21037/jtd.2018.04.74 　

    ISSN： 2077-6624 2072-1439

  42. Concurrent Community Transmission of Enterovirus D68 With Human Rhinoviruses and Respiratory Syncytial Virus Among Children in Sendai, Japan. Peer-reviewed

    Metoki T, Okamoto M, Suzuki A, Kitaoka S, Miyabayashi H, Rokugo Y, Onuma R, Noguchi R, Sato T, Watanabe Y, Ohmiya S, Sato K, Nishimura H, Oshitani H, Kumaki S

    The Pediatric infectious disease journal　37　(5)　394-400　2018/05

    DOI： 10.1097/INF.0000000000001768 　

    ISSN： 0891-3668

  43. Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines. International-journal Peer-reviewed

    Hideki Hayashi, Yoshinao Kubo, Mai Izumida, Etsuhisa Takahashi, Hiroshi Kido, Ko Sato, Mutsuo Yamaya, Hidekazu Nishimura, Kou Nakayama, Toshifumi Matsuyama

    Frontiers in cellular and infection microbiology　8　91-91　2018

    DOI： 10.3389/fcimb.2018.00091 　

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    Cleavage and activation of hemagglutinin (HA) by trypsin-like proteases in influenza A virus (IAV) are essential prerequisites for its successful infection and spread. In host cells, some transmembrane serine proteases such as TMPRSS2, TMPRSS4 and HAT, along with plasmin in the bloodstream, have been reported to cleave the HA precursor (HA0) molecule into its active forms, HA1 and HA2. Some trypsinogens can also enhance IAV proliferation in some cell types (e.g., rat cardiomyoblasts). However, the precise activation mechanism for this process is unclear, because the expression level of the physiological activator of the trypsinogens, the TMPRSS15 enterokinase, is expected to be very low in such cells, with the exception of duodenal cells. Here, we show that at least two variant enterokinases are expressed in various human cell lines, including A549 lung-derived cells. The exogenous expression of these enterokinases was able to enhance the proliferation of IAV in 293T human kidney cells, but the proliferation was reduced by knocking down the endogenous enterokinase in A549 cells. The enterokinase was able to enhance HA processing in the cells, which activated trypsinogen in vitro and in the IAV-infected cells also. Therefore, we conclude that enterokinase plays a role in IAV infection and proliferation by activating trypsinogen to process viral HA in human cell lines.

  44. Efficient isolation of human metapneumovirus using MNT-1, a human malignant melanoma cell line with early and distinct cytopathic effects Peer-reviewed

    Ko Sato, Oshi Watanabe, Suguru Ohmiya, Fumiko Chiba, Akira Suzuki, Michiko Okamoto, Jiang Younghuang, Akihiro Hata, Hiroyuki Nonaka, Setsuko Kitaoka, Yukio Nagai, Kazuhisa Kawamura, Masahiro Hayashi, Satoru Kumaki, Tamio Suzuki, Kazuyoshi Kawakami, Hidekazu Nishimura

    MICROBIOLOGY AND IMMUNOLOGY　61　(11)　497-506　2017/11

    DOI： 10.1111/1348-0421.12542 　

    ISSN： 0385-5600

    eISSN： 1348-0421

  45. クリプトコックス感染における宿主認識と生体防御機構 Invited Peer-reviewed

    佐藤 光, 川上 和義

    Medical Mycology Journal　58　(3)　J83-J90　2017/07

    Publisher: (一社)日本医真菌学会

    ISSN： 2185-6486

    eISSN： 2186-165X

  46. Comparison of sensitivity among commercially available kits for the detection of human metapneumovirus antigen Peer-reviewed

    大宮卓, 佐藤光, 佐々木純一, 西村秀一

    医学検査　66　(3)　212‐216-323　2017/05

    Publisher: Japanese Association of Medical Technologists

    DOI： 10.14932/jamt.17-45 　

    ISSN： 0915-8669

    More details Close

    A comparison of sensitivity was performed among adenovirus antigen detection kits, which were developed on the basis of immunochromatography technology and are routinely used in the clinical setting. The tested kits were QuicknaviTM-Adeno, Quickchaser®Adeno, Immunocard®ST AdenovirusⅡ, BD VeritorTMSystem Adeno, Primecheck®Adeno, and Imunoace®Adeno. The comparison was performed with 8 standard strains of adenovirus stocks, namely, types 1–7 and 11, as the subjects for the test. The minimum detection limit of concentration of each kit was determined comparatively for each viral strain by investigating the maximum dilution rate of the viral stock giving a positive result. Thus, the concentration limit differed among viral strains for each kit and among kits for each viral strain, showing even a 50-fold difference in extreme cases. Particularly for adenovirus types 6 and 11, all the tested kits showed poor reactivity. Then, the absolute minimum detection limits were calculated on the basis of the minimum copy number of viral DNA or the minimum detectable infective titer of the subject strains to the culture cells. Greater differences were found in the comparison among viral strains when using the infectivity than when using the gene copy numbers: the infectivity titers of the virus stocks of types 3, 7, and 11 were about 107 times lower than those of other strains, and the sensitivities to types 3, 7, and 11 were found to be apparently higher than those to other types when the infectivity was used for the comparison. Thus, caution is advised in comparisons using the infectivity parameter, and gene copy number could be a preferable alternative.

  47. Efficient isolation of human parainfluenza viruses 1 and 3 using MNT-1, a human malignant melanoma cell line system that exhibits an apparent cytopathic effect Peer-reviewed

    Ko Sato, Oshi Watanabe, Suguru Ohmiya, Fumiko Chiba, Masahiro Hayashi, Tamio Suzuki, Kazuyoshi Kawakami, Hidekazu Nishimura

    MICROBIOLOGY AND IMMUNOLOGY　60　(11)　801-805　2016/11

    DOI： 10.1111/1348-0421.12446 　

    ISSN： 0385-5600

    eISSN： 1348-0421

  48. Characterization of an A (H1N1)pdm09 Virus Imported from India in March 2015 Peer-reviewed

    Emi Takashita, Seiichiro Fujisaki, Masayuki Shirakura, Kazuya Nakamura, Noriko Kishida, Tomoko Kuwahara, Suguru Ohmiya, Ko Sato, Hiroko Ito, Fumiko Chiba, Hidekazu Nishimura, Shizuo Shindo, Shinji Watanabe, Takato Odagiri

    JAPANESE JOURNAL OF INFECTIOUS DISEASES　69　(1)　83-86　2016/01

    DOI： 10.7883/yoken.JJID.2015.460 　

    ISSN： 1344-6304

    eISSN： 1884-2836

  49. Infectivity Titers of Each Component of the Influenza Virus in the Live Vaccine Purchased from a Parallel Import Distributing System

    SATO Ko, KIKUCHI Yuki, MASAGO Yoshifumi, OHMIYA Suguru, ITO Hiroko, KIMURA Tastuo, NISHIMURA Hidekazu

    Kansenshogaku Zasshi　89　(6)　720-726　2015/11

    Publisher: The Japanese Association for Infectious Diseases

    DOI： 10.11150/kansenshogakuzasshi.89.720 　

    ISSN： 0387-5911

  50. Cryptococcus neoformans Infection in Mice Lacking Type I Interferon Signaling Leads to Increased Fungal Clearance and IL-4-Dependent Mucin Production in the Lungs Peer-reviewed

    Ko Sato, Hideki Yamamoto, Toshiki Nomura, Ikumi Matsumoto, Tomomitsu Miyasaka, Tong Zong, Emi Kanno, Kazuko Uno, Keiko Ishii, Kazuyoshi Kawakami

    PLOS ONE　10　(9)　e0138291　2015/09

    DOI： 10.1371/journal.pone.0138291 　

    ISSN： 1932-6203

  51. Dectin-2 Deficiency Promotes Th2 Response and Mucin Production in the Lungs after Pulmonary Infection with Cryptococcus neoformans Peer-reviewed

    Yuri Nakamura, Ko Sato, Hideki Yamamoto, Kana Matsumura, Ikumi Matsumoto, Toshiki Nomura, Tomomitsu Miyasaka, Keiko Ishii, Emi Kanno, Masahiro Tachi, Sho Yamasaki, Shinobu Saijo, Yoichiro Iwakura, Kazuyoshi Kawakami

    INFECTION AND IMMUNITY　83　(2)　671-681　2015/02

    DOI： 10.1128/IAI.02835-14 　

    ISSN： 0019-9567

    eISSN： 1098-5522

  52. Low-dose maintenance gemcitabine-carboplatin chemotherapy could be an alternative to continuous standard chemotherapy for patients with metastatic urothelial carcinoma Peer-reviewed

    Koji Mitsuzuka, Shinichi Yamashita, Shunichi Namiki, Shigeyuki Yamada, Ko Sato, Hideo Saito, Yasuhiro Kaiho, Akihiro Ito, Haruo Nakagawa, Yoichi Arai

    INTERNATIONAL JOURNAL OF UROLOGY　21　(11)　1114-1119　2014/11

    DOI： 10.1111/iju.12532 　

    ISSN： 0919-8172

    eISSN： 1442-2042

  53. Defect of CARD9 Leads to Impaired Accumulation of Gamma Interferon-Producing Memory Phenotype T Cells in Lungs and Increased Susceptibility to Pulmonary Infection with Cryptococcus neoformans Peer-reviewed

    Hideki Yamamoto, Yuri Nakamura, Ko Sato, Yurie Takahashi, Toshiki Nomura, Tomomitsu Miyasaka, Keiko Ishii, Hiromitsu Hara, Natsuo Yamamoto, Emi Kanno, Yoichiro Iwakura, Kazuyoshi Kawakami

    INFECTION AND IMMUNITY　82　(4)　1606-1615　2014/04

    DOI： 10.1128/IAI.01089-13 　

    ISSN： 0019-9567

    eISSN： 1098-5522

  54. Involvement of Gr-1(dull+) Cells in the Production of TNF-alpha and IL-17 and Exacerbated Systemic Inflammatory Response Caused by Lipopolysaccharide Peer-reviewed

    Daiki Tanno, Yukiko Akahori, Masahiko Toyama, Ko Sato, Daisuke Kudo, Yuzuru Abe, Tomomitsu Miyasaka, Hideki Yamamoto, Keiko Ishii, Emi Kanno, Ryoko Maruyama, Shigeki Kushimoto, Yoichiro Iwakura, Kazuyoshi Kawakami

    INFLAMMATION　37　(1)　186-195　2014/02

    DOI： 10.1007/s10753-013-9729-5 　

    ISSN： 0360-3997

    eISSN： 1573-2576

Show all ︎Show first 5

Misc. 64

  1. クリプトコックス潜在性感染マウスモデルにおけるFTY720投与による内因性再燃の免疫機序の解明

    西田朱里, 佐藤光, 吉田美智子, 青柳哲史, 青柳哲史, 川上和義

    日本医真菌学会雑誌　66　(Supplement 1)　2025

    ISSN： 2434-5229

  2. クリプトコックス莢膜多糖合成に関与する新規糖転移酵素Cgm1の病原性の解析

    鈴木亜里紗, 佐藤光, 田中大, 佐々木雅人, 青柳哲史, 青柳哲史, 川上和義

    日本医真菌学会雑誌　66　(Supplement 1)　2025

    ISSN： 2434-5229

  3. Analysis of the exacerbation of cryptococcal infection and the underlying immune mechanisms in diabetic mice

    佐藤光, 神林直希, 丹野寛大, 菅野恵美, 青柳哲史, 青柳哲史, 石井恵子, 川上和義

    日本生体防御学会学術総会講演抄録集　35th (Web)　2024

  4. クリプトコックス潜在性感染マウスモデルを用いたFingolimod(FTY720)投与による内因性再燃の免疫機序の解明

    吉田 美智子, 中畑 那奈, 篠宮 岳志, 佐藤 光, 菅野 恵美, 丹野 寛大, 石井 恵子, 青柳 哲史, 菊池 敦生, 川上 和義

    日本小児感染症学会総会・学術集会プログラム・抄録集　55回　183-183　2023/11

    Publisher: (一社)日本小児感染症学会

  5. 真菌検査における新しい潮流 クリプトコックスの潜在性感染診断のためのIGRA法の開発

    佐藤 光, 川上 和義

    日本医真菌学会雑誌　63　(Suppl.1)　73-73　2022/09

    Publisher: (一社)日本医真菌学会

    ISSN： 2434-5229

  6. 真菌感染症の近未来 クリプトコックス症に対するワクチン開発の現状と展望

    佐藤 光, 川上 和義

    日本医真菌学会雑誌　63　(Suppl.1)　90-90　2022/09

    Publisher: (一社)日本医真菌学会

    ISSN： 2434-5229

  7. 検体の低温保管がRSV分離へ与える影響の検討

    北井 優貴, 大宮 卓, 竹田 誠, 西村 秀一, 白戸 憲也, 佐藤 光, 川上 和義

    臨床とウイルス　50　(2)　108-108　2022/05

    Publisher: 日本臨床ウイルス学会

    ISSN： 0303-8092

  8. 米国CDCによって開発されたヒトRSウイルスのリアルタイムRT-PCR検出系の国内小児入院患者検体を用いた実際的検証

    白戸憲也, 諏訪麗子, 久米庸平, 川瀬みゆき, 知識美奈, 小野貴志, 則藤桜子, 佐藤光, 岡本道子, 久間木悟, 永井幸夫, 細矢光亮, 竹田誠, 西村秀一, 橋本浩一

    日本ウイルス学会学術集会プログラム・予稿集(Web)　69th　2022

  9. 最新のワクチン開発事情 肺炎球菌ワクチンの現状と今後の展開

    佐藤 光, 川上 和義

    日本化学療法学会雑誌　70　(1)　118-119　2022/01

    Publisher: (公社)日本化学療法学会

    ISSN： 1340-7007

    eISSN： 1884-5886

  10. 肺炎球菌感染におけるPlacenta-expressed transcript 1の機能解析

    笠松 純, 岩岡 大貴, 篠宮 岳志, 佐藤 光, 石井 恵子, 川上 和義

    感染症学雑誌　95　(臨増)　205-205　2021/04

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

    eISSN： 1884-569X

  11. クリプトコックス感染防御におけるClaudin欠損の影響

    佐藤 光, 笠松 純, 篠宮 岳志, 山本 秀輝, 石井 恵子, 川上 和義

    感染症学雑誌　95　(臨増)　206-206　2021/04

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

    eISSN： 1884-569X

  12. 肺炎球菌酸化鉄ナノ粒子ワクチンによる抗体産生 Poly(I:C)のアジュバント効果の解析

    岩岡 大貴, 高倉 直幸, 佐藤 光, 笠松 純, 石井 恵子, 川上 和義

    感染症学雑誌　95　(臨増)　229-229　2021/04

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

    eISSN： 1884-569X

  13. Poly(I:C)をアジュバントとしたクリプトコックス酸化鉄ナノ粒子ワクチンによるTh1型抗体産生の誘導

    篠宮 岳志, 梅木 彩, 佐藤 光, 笠松 純, 石井 恵子, 川上 和義

    感染症学雑誌　95　(臨増)　245-245　2021/04

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

    eISSN： 1884-569X

  14. Recent molecular evolution of human metapneumovirus and subdivision of A2 subtype

    直亨則, 直亨則, 七種美和子, 佐藤光, 関塚剛史, 宇宿秀三, 田中伸子, 西村秀一, 竹田誠

    日本ウイルス学会学術集会プログラム・予稿集(Web)　68th　2021

  15. 肺炎球菌酸化鉄ナノ粒子ワクチンによる抗体産生:Poly(I:C)のアジュバント効果の解析

    岩岡大貴, 高倉直幸, 佐藤光, 笠松純, 石井恵子, 川上和義, 川上和義

    日本化学療法学会雑誌　69　(Supplement-A)　2021

    ISSN： 1340-7007

  16. 肺炎球菌感染におけるPlacenta-expressed transcript1の機能解析

    笠松純, 岩岡大貴, 篠宮岳志, 佐藤光, 石井恵子, 川上和義, 川上和義

    日本化学療法学会雑誌　69　(Supplement-A)　2021

    ISSN： 1340-7007

  17. Poly(I:C)をアジュバントとしたクリプトコックス酸化鉄ナノ粒子ワクチンによるTh1型抗体産生の誘導

    篠宮岳志, 梅木彩, 佐藤光, 笠松純, 石井恵子, 川上和義, 川上和義

    日本化学療法学会雑誌　69　(Supplement-A)　2021

    ISSN： 1340-7007

  18. クリプトコックス感染防御におけるClaudin欠損の影響

    佐藤光, 笠松純, 篠宮岳志, 山本秀輝, 石井恵子, 川上和義, 川上和義

    日本化学療法学会雑誌　69　(Supplement-A)　2021

    ISSN： 1340-7007

  19. NTMと肺真菌症 クリプトコックスの内因性再燃発症の可能性 結核との類似性

    佐藤 光, 川上 和義

    結核　95　(5)　86-86　2020/09

    Publisher: (一社)日本結核・非結核性抗酸菌症学会

    ISSN： 0022-9776

    eISSN： 1884-2410

  20. 真菌・細菌感染防御と肉芽腫・多核巨細胞 クリプトコックス及び結核菌感染に対するTh1免疫応答を介した感染防御機構

    佐藤 光, 川上 和義

    日本医真菌学会雑誌　61　(Suppl.)　46-46　2020/09

    Publisher: (一社)日本医真菌学会

    ISSN： 2434-5229

  21. クリプトコックス感染防御におけるClaudins欠損の影響

    佐藤 光, 笠松 純, 山本 秀輝, 石井 恵子, 川上 和義

    日本医真菌学会雑誌　61　(Suppl.)　81-81　2020/09

    Publisher: (一社)日本医真菌学会

    ISSN： 2434-5229

  22. グルコシルセラミドを標的としたクリプトコックスワクチン開発のための基礎的検討

    笠松 純, 佐藤 光, 北井 優貴, 川上 和義

    日本医真菌学会雑誌　61　(Suppl.)　81-81　2020/09

    Publisher: (一社)日本医真菌学会

    ISSN： 2434-5229

  23. 毎年連続のインフルエンザ不活化ワクチンの接種によるウイルスNA蛋白質に対する抗体獲得についての検討

    木須 友子, 伊藤 洋子, 大宮 卓, 西村 秀一, 佐藤 光

    宮城県公衆衛生学会会誌　(52)　16-16　2020/04

    Publisher: 宮城県公衆衛生学会

    ISSN： 0912-747X

  24. クリプトコックス感染の自然免疫時相におけるIFN-γ産生機構の解析

    梅木 彩, 中畑 那奈, 篠宮 岳志, 佐藤 光, 笠松 純, 山本 秀輝, 石井 恵子, 川上 和義

    感染症学雑誌　94　(2)　273-273　2020/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  25. クリプトコックス感染の自然免疫時相におけるメモリー、エフェクターT細胞からのIFN-γ産生

    中畑 那奈, 梅木 彩, 佐藤 光, 笠松 純, 山本 秀輝, 石井 恵子, 川上 和義

    感染症学雑誌　94　(臨増)　292-292　2020/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  26. クリプトコックス感染防御におけるTight junctionタンパク質欠損の影響

    佐藤 光, 笠松 純, 山本 秀輝, 石井 恵子, 川上 和義

    感染症学雑誌　94　(臨増)　292-292　2020/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  27. 「臨床的課題を基礎からサイエンスし解決策を探る」-インフルエンザと続発性細菌性肺炎を例として- 肺炎球菌に対する免疫認識機序と肺炎の発症病態 新規ワクチン開発への展開を含めて

    佐藤 光, 川上 和義

    感染症学雑誌　94　(臨増)　119-119　2020/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  28. グルコシルセラミドを標的としたクリプトコックス症のワクチン開発を目指した基礎研究

    笠松純, 佐藤光, 北井優貴, 石井恵子, 川上和義

    日本感染症学会東日本地方会学術集会・日本化学療法学会東日本支部総会合同学会プログラム・抄録集　69th-67th　2020

  29. Characterization and function of intestinal eosinophil subsets

    笠松純, 笠松純, 城下智, 佐藤光, 川上和義, 川上和義, COLONNA Marco

    日本細菌学雑誌(Web)　75　(1)　2020

    ISSN： 1882-4110

  30. 感染と免疫の分子機構 腸管好酸球サブセットの同定と機能

    笠松 純, 城下 智, 佐藤 光, 川上 和義, Colonna Marco

    日本細菌学雑誌　75　(1)　7-7　2020/01

    Publisher: 日本細菌学会

    ISSN： 0021-4930

    eISSN： 1882-4110

  31. クリプトコックス感染におけるIL-17AによるTh1免疫応答の制御と防御機構への影響

    佐藤 光, 笠松 純, 山本 秀輝, 石井 恵子, 川上 和義

    日本医真菌学会雑誌　60　(Suppl.1)　87-87　2019/10

    Publisher: (一社)日本医真菌学会

    ISSN： 2434-5229

  32. 培養細胞への感染性におけるヒトメタニューモウイルス株間の一致と差異

    竹田 誠, 直 亨則, 佐藤 光, 西村 秀一

    日本小児感染症学会総会・学術集会プログラム・抄録集　51回　142-142　2019/10

    Publisher: 日本小児感染症学会

  33. クリプトコックス感染におけるIL-17AによるTh1免疫応答の制御と防御機構への影響

    佐藤 光, 笠松 純, 山本 秀輝, 石井 恵子, 川上 和義

    日本医真菌学会雑誌　60　(Suppl.1)　87-87　2019/10

    Publisher: (一社)日本医真菌学会

    ISSN： 2434-5229

  34. 免疫療法 真菌より見出したオリゴDNAによるTh2免疫抑制を介した気管支喘息の制御

    鈴木 柊伍, 平田 大実, 宮坂 智充, 佐藤 光, 笠松 純, 石井 恵子, 川上 佳織, 高橋 知子, 大野 勲, 川上 和義

    アレルギー　68　(4-5)　516-516　2019/05

    Publisher: (一社)日本アレルギー学会

    ISSN： 0021-4884

    eISSN： 1347-7935

  35. クリプトコックス内因性再燃モデルマウスの作成と免疫機序の解析

    梅木 彩, 笠松 純, 佐藤 光, 臼田 薫, 石井 恵子, 川上 和義

    感染症学雑誌　93　(臨増)　323-323　2019/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  36. クリプトコックス感染におけるIL-17Aを介したTh1免疫応答の制御と防御機構への影響

    佐藤 光, 山本 秀輝, 石井 恵子, 川上 和義

    感染症学雑誌　93　(臨増)　323-323　2019/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  37. 家族内感染が推測されたヒトメタニューモウイルス(Human metapneumovirus:hMPV)症例の後ろ向き観察研究

    生方 智, 木村 望, 神宮 大輔, 矢島 剛洋, 庄司 淳, 高橋 洋, 佐藤 光, 西村 秀一

    感染症学雑誌　93　(臨増)　332-332　2019/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  38. Antibody production and host protection by novel pneumococcal nanoparticle vaccine

    中平絢子, 岩岡大貴, 佐藤光, 笠松純, 石井恵子, 川上和義, 川上和義

    日本生体防御学会学術総会講演抄録集　30th　2019

  39. 当科で経験したパラインフルエンザウイルス感染症285例の検討

    三浦 拓人, 鈴木 聡志, 石田 智之, 渡邉 浩司, 渡邊 庸平, 加賀 麻衣子, 大沼 良一, 貴田岡 節子, 佐藤 光, 大宮 卓, 渡邊 王志, 西村 秀一, 久間木 悟

    日本小児科学会雑誌　122　(6)　1108-1108　2018/06

    Publisher: (公社)日本小児科学会

    ISSN： 0001-6543

  40. ヒトメタニューモウイルスの分離用に新たに見出した培養細胞の有用性の検討

    佐藤 光, 渡邊 王志, 大宮 卓, 千葉 ふみ子, 貴田岡 節子, 久間木 悟, 永井 幸夫, 林 昌浩, 鈴木 民夫, 川上 和義, 西村 秀一

    宮城県公衆衛生学会会誌　(50)　24-24　2018/03

    Publisher: 宮城県公衆衛生学会

    ISSN： 0912-747X

  41. 当科で経験したパラインフルエンザウイルス感染症285例の検討

    三浦 拓人, 鈴木 聡志, 石田 智之, 渡邊 浩司, 渡邊 庸平, 加賀 麻衣子, 大沼 良一, 貴田岡 節子, 佐藤 光, 大宮 卓, 渡邊 王志, 西村 秀一, 久間木 悟

    日本小児科学会雑誌　122　(2)　300-300　2018/02

    Publisher: (公社)日本小児科学会

    ISSN： 0001-6543

  42. ヒトメタニューモウイルスの分離用に新たに見出した培養細胞の有用性の検討

    佐藤 光, 大宮 卓, 渡辺 王志, 千葉 ふみ子, 西村 秀一

    医療の広場　57　(10)　23-26　2017/10

    Publisher: (公財)政策医療振興財団

    More details Close

    ヒト悪性黒色腫由来のMNT-1細胞について、ヒトメタニューモウイルス(HMPV)の分離効率を従来使用してきた細胞と比較し、同細胞がHMPV分離に効果的か検討を行った。MNT-1、LLC-MK2、Vero E6細胞を用いた。HMPVを検出した鼻腔ぬぐい液を細胞に接種した。MNT-1細胞は、これまで用いられてきた細胞と比べ、より効率的にHMPVを分離できる可能性が示唆された。RT-PCR法にてHMPVを検出した臨床検体25例を対象とした。MNT-1細胞は他の2種類の細胞と比べ、より多くのウイルスを分離できた。さらに、分離にかかる時間も、より早かった。急性呼吸器感染症(ARI)の疑い患者より採取した鼻腔・咽頭ぬぐい液1335件を対象とした。MNT-1、LLC-MK2細胞を含む6種類の培養細胞を用いたマイクロプレート法でウイルス分離を行い、計27株(2.2%)のHMPVを分離した。2016年、仙台市内においてHMPVは1月から7月にかけて流行がみられ、A1型は検出されず、A2型が中心のB1、B2型も検出される混合流行であった。

  43. パラインフルエンザウイルスに対する既存のプロテアーゼ阻害薬の増殖抑制効果の検討

    飯野 佑佳, 佐藤 光, 山谷 睦雄, 磯貝 恵美子, 西村 秀一

    感染症学雑誌　91　(臨増)　291-291　2017/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  44. 当科で経験したエンテロウイルスD68(EV-D68)感染症17例の臨床的検討 RSウイルス感染症32例との比較

    目時 嵩也, 三浦 舞子, 宮林 広樹, 六郷 由佳, 佐藤 大記, 渡邊 庸平, 野口 里恵, 大沼 良一, 渡邉 浩司, 貴田岡 節子, 久間木 悟, 岡本 道子, 押谷 仁, 大宮 卓, 佐藤 光, 西村 秀一, 鈴木 陽

    日本小児科学会雑誌　121　(1)　123-123　2017/01

    Publisher: (公社)日本小児科学会

    ISSN： 0001-6543

  45. Recognition of Cryptococcus neoformans by Pattern Recognition Receptors and its Role in Host Defense to This Infection.

    Ko Sato, Kazuyoshi Kawakami

    Medical mycology journal　58　(3)　J83-J90-J90　2017

    Publisher: (一社)日本医真菌学会

    DOI： 10.3314/mmj.17.011 　

    ISSN： 2185-6486

    More details Close

    Cryptococcus neoformans is a yeast-type opportunistic fungal pathogen with a capsule structure consisting of polysaccharides, such as glucuronoxylomannan and galactoxylomannan, and infects the lungs via an air-borne route. Most healthy individuals undergo asymptomatic infection with granulomatous lesions in the lungs caused by C. neoformans. However, immunocompromised hosts with severely impaired cellular immunity, such as those with acquired immune deficiency syndrome (AIDS), often suffer from disseminated infection into the central nervous system, leading to life-threatening meningoencephalitis. The recognition of pathogen-associated molecular patterns (PAMPs) by macrophages and dendritic cells plays an important role as the first line of host defense in the elimination of pathogens. Recently, numerous pattern recognition receptors (PRRs) that recognize these PAMPs have been identified. Also, the involvement of these PRRs, such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and C-type lectin receptors (CLRs), in cryptococcal infection has been analyzed. In particular, TLR9, NLR family pyrin domain-containing 3 (NLRP3), Dectin-2, mannose receptor (MR), and DC-SIGN have been found to recognize the DNA, cell wall components, intracellular polysaccharides, and mannoproteins, respectively. Future studies are expected to promote elucidation of the mechanisms of host immune response to C. neoformans, which will lead to the development of new vaccines and therapies for cryptococcal infection.

  46. 真菌感染防御と糖鎖認識 C-type lectin receptorsによるクリプトコックスの認識と感染防御

    佐藤 光, 川上 和義, 中村 優里, 山本 秀輝, 丹野 大樹, 石井 恵子, 山崎 晶, 岩倉 洋一郎, 原 博満, 西城 忍

    Medical Mycology Journal　57　(Suppl.1)　76-76　2016/09

    Publisher: (一社)日本医真菌学会

    ISSN： 2185-6486

    eISSN： 2186-165X

  47. Veno-Venous Extracorporeal Membrane Oxygenation(V-V ECMO)管理で救命しえた重症呼吸不全の乳児例

    渡邉 知佳, 青柳 順, 今川 智之, 小高 淳, 中村 文人, 多賀 直行, 大宮 卓, 佐藤 光, 西村 秀一, 久保 亨, 森内 浩幸, 蒲地 一成, 田村 大輔, 山形 崇倫

    日本小児呼吸器学会雑誌　27　(Suppl.)　150-150　2016/09

    Publisher: 日本小児呼吸器学会

    ISSN： 2187-5731

  48. パラインフルエンザウイルスの分離におけるMNT-1細胞の有用性の検討

    佐藤 光, 大宮 卓, 西村 秀一

    臨床とウイルス　44　(2)　S63-S63　2016/05

    Publisher: 日本臨床ウイルス学会

    ISSN： 0303-8092

  49. B型インフルエンザウイルスの増殖に対するセリンプロテアーゼ阻害剤camostatおよびnafamostatの抑制効果

    井出 杏実, 西村 秀一, 大宮 卓, 佐藤 光

    臨床とウイルス　44　(2)　S80-S80　2016/05

    Publisher: 日本臨床ウイルス学会

    ISSN： 0303-8092

  50. マイクロプレートを利用した低容量のNA活性測定法の確立とその応用

    伊藤 洋子, 大宮 卓, 佐藤 光, 西村 秀一

    臨床とウイルス　44　(2)　S81-S81　2016/05

    Publisher: 日本臨床ウイルス学会

    ISSN： 0303-8092

  51. 胃の消化不良症状に始まり軽度の下痢症状に終わったサポウイルス感染の成人男性の一症例の詳細

    西村 秀一, 佐藤 光, 大宮 卓, 鵜飼 克明, 植木 洋, 岡本 道子

    感染症学雑誌　90　(臨増)　259-259　2016/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  52. 仙台市における2015年9月から10月のエンテロウイルスD68を含む呼吸器ウイルスの流行

    岡本 道子, 大宮 卓, 佐藤 光, 伊藤 洋子, 西村 秀一, 押谷 仁, 久間木 悟, 貴田岡 節子

    感染症学雑誌　90　(臨増)　266-266　2016/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  53. クリプトコックス感染におけるTh1依存性防御応答のIL-17Aによる制御

    景澤 貴史, 野村 俊樹, 佐藤 光, 山本 秀樹, 松本 郁美, 横山 隣, 石井 恵子, 岩倉 洋一郎, 川上 和義

    感染症学雑誌　90　(臨増)　329-329　2016/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  54. 仙台市内小児科医療定点における薬剤耐性インフルエンザウイルスのモニタリング

    鈴木 陽, 佐藤 光, 大宮 卓, 西村 秀一, 久間木 悟, 貴田岡 節子, 永井 幸夫

    宮城県公衆衛生学会会誌　(48)　13-13　2016/03

    Publisher: 宮城県公衆衛生学会

    ISSN： 0912-747X

  55. CT画像上、急性副鼻腔炎症の併発が確認された成人男性のRSウイルス感染症の一症例

    西村 秀一, 佐藤 光, 大宮 卓, 伊藤 洋子, 久保 亨

    感染症学雑誌　90　(臨増)　274-274　2016/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  56. 健常成人における家族内伝播と考えられたヒトメタニューモウイルス(hMPV)感染症の1家族例

    生方 智, 高橋 洋, 矢島 剛洋, 神宮 大輔, 庄司 淳, 佐藤 光, 西村 秀一

    感染症学雑誌　90　(臨増)　294-294　2016/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  57. 並行輸入された経鼻インフルエンザ生ワクチン,フルミストに含まれるウイルスの感染価の解析

    佐藤光, 佐藤光, 菊地佑樹, 真砂佳史, 大宮卓, 伊藤洋子, 大村達夫, 西村秀一

    感染症学雑誌　90　(臨増)　277-277　2016/03

    Publisher: (一社)日本感染症学会

    ISSN： 0387-5911

  58. 並行輸入された経鼻インフルエンザ生ワクチンに含まれるウイルスの感染価の解析

    佐藤光, 菊地佑樹, 真砂佳史, 大宮卓, 伊藤洋子, 大村達夫, 西村秀一

    日本ワクチン学会学術集会プログラム・抄録集　19th　138　2015

  59. 高齢化する進行尿路上皮癌患者 治療戦略の再考 進行性尿路上皮癌に対するメトロノミックGemcitabin-Carboplatin化学療法の試み

    三塚 浩二, 安達 尚宣, 並木 俊一, 山田 成幸, 佐藤 光, 齋藤 英郎, 海法 康裕, 伊藤 明宏, 中川 晴夫, 荒井 陽一

    日本泌尿器科学会総会　102回　377-377　2014/04

    Publisher: (一社)日本泌尿器科学会総会事務局

  60. 免疫細胞のCryptococcus neoformans認識におけるC-type lectin receptorsの役割 Mincleを中心とした検討

    松村 香菜, 佐藤 光, 石井 恵子, 安達 禎之, 大野 尚仁, 川上 和義, 中村 優里, 山本 秀輝, 館 正弘, 山崎 晶, 原 博満

    Medical Mycology Journal　54　(Suppl.1)　83-83　2013/09

    Publisher: (一社)日本医真菌学会

    ISSN： 2185-6486

    eISSN： 2186-165X

  61. Cryptococcus neoformans感染免疫応答における1型インターフェロン受容体欠損の影響

    佐藤 光, 松村 香菜, 石井 恵子, 川上 和義, 山本 秀輝

    Medical Mycology Journal　54　(Suppl.1)　83-83　2013/09

    Publisher: (一社)日本医真菌学会

    ISSN： 2185-6486

  62. 免疫細胞のCryptococcus neoformans認識におけるC-type lectin receptorsの役割 Mincleを中心とした検討

    松村 香菜, 佐藤 光, 石井 恵子, 安達 禎之, 大野 尚仁, 川上 和義, 中村 優里, 山本 秀輝, 館 正弘, 山崎 晶, 原 博満

    Medical Mycology Journal　54　(Suppl.1)　83-83　2013/09

    Publisher: (一社)日本医真菌学会

    ISSN： 2185-6486

  63. Essential role of Card9 in innate IFN-gamma production and Th17 differentiation in the host defense against cryptococcal infection

    H. Yamamoto, Y. Nakamura, K. Sato, K. Matsumura, N. Yamamoto, K. Ishii, H. Hara, K. Kawakami

    INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS　42　S126-S126　2013/06

    ISSN： 0924-8579

  64. Signaling via an adapter molecule CARD9 is essential for the host defense to infection with Cryptococcus neoformans

    Hideki Yamamoto, Yuri Nakamura, Yurie Takahashi, Ko Sato, Natsuo Yamamoto, Keiko Ishii, Hiromitsu Hara, Kazuyoshi Kawakami

    JOURNAL OF IMMUNOLOGY　188　2012/05

    ISSN： 0022-1767

Show all ︎Show first 5

Books and Other Publications 3

  1. 病理学

    鈴木, 貴, 菅野, 恵美

    南江堂　2025/08

    ISBN: 9784524210251

  2. Step forward医療系学生のための基礎生物学 = Step forward basic biology for students learning about healthcare sciences

    仲田, 栄子, 小林, 純也, 飯島, 典生

    メジカルビュー社　2025/07

    ISBN: 9784758322768

  3. ウイルス検査法 臨床と検査室のための手引き

    春恒社　2018/09

Presentations 41

  1. 潜在性クリプトコックス感染から内因性再燃を制御する予防・診断・治療法に関する研究 Invited

    佐藤光

    第5回日本医学会連合 Rising Starリトリート　2026/05/28

  2. 免疫を軸とした感染症研究 ～臨床につながる基礎研究～ Invited

    佐藤光

    第74回日本感染症学会東日本地方会学術集会・第72回日本化学療法学会東日本支部総会 合同学会　2025/09/25

  3. 酸化鉄ナノ粒子を基盤とした新規肺炎球菌ワクチンによるNKT細胞を介したIgA産生誘導メカニズムの解析

    岩岡大貴, 中平絢子, 佐藤光, 明田幸弘, 大石和徳, 丹野寛大, 菅野恵美, 石井恵子, 川上和義, 青柳哲史

    第77回日本細菌学会東北支部総会・学術集会　2025/08/21

  4. Analysis of latent cryptococcal infection and reactivation using a novel mouse model Invited

    the 96th annual meeting of japanese society for bacteriology　2023/03/18

  5. クリプトコックス症に対するワクチン開発の現状と展望 Invited

    佐藤光, 川上和義

    第66回日本医真菌学会総会・学術集会　2022/10/02

  6. クリプトコックスの潜在性感染診断のためのIGRA法の開発 Invited

    佐藤光, 川上和義

    第66回日本医真菌学会総会・学術集会　2022/10/01

  7. クリプトコックス感染防御における免疫応答の解析 Invited

    佐藤光

    第32回日本生体防御学会学術総会　2021/09/07

  8. クリプトコックス感染防御におけるClaudin欠損の影響

    佐藤光, 笠松純, 篠宮岳志, 山本秀輝, 石井恵子, 川上和義

    第95回日本感染症学会学術講演会・第69回日本化学療法学会総会　2021/05/07

  9. クリプトコックス感染防御におけるMincleの役割

    佐藤光, 笠松純, 佐藤祐樹, 菅野恵美, 丹野寛大, 石井恵子, 川上和義

    第4回東北医真菌研究会　2020/12/20

  10. クリプトコックスの内因性再燃発症の可能性：結核との類似性 Invited

    佐藤光, 川上和義

    第95回日本結核・非結核性抗酸菌症学会総会・学術講演会　2020/10/12

  11. クリプトコックス感染防御におけるClaudins欠損の影響

    佐藤光, 笠松純, 山本秀輝, 石井恵子, 川上和義

    第64回日本医真菌学会総会・学術集会　2020/10/10

  12. クリプトコックス及び結核菌感染に対するTh1免疫応答を介した感染防御機構 Invited

    佐藤光, 川上和義

    第64回日本医真菌学会総会・学術集会　2020/10/10

  13. クリプトコックス感染防御におけるTight junctionタンパク質欠損の影響

    佐藤光, 笠松純, 山本秀輝, 石井恵子, 川上和義

    第94回日本感染症学会総会・学術講演会

  14. 肺炎球菌に対する免疫認識機序と肺炎の発症病態ー新規ワクチン開発への展望を含めて Invited

    佐藤光, 川上和義

    第94回日本感染症学会総会・学術講演会　2020/08/19

  15. クリプトコックスの潜在性感染・内因性再燃診断のためのIGRA法の開発 Invited

    佐藤光, 笠松純, 石井恵子, 川上和義

    MSD生命科学財団 研究助成 4領域合同 研究発表会　2020/02/16

  16. クリプトコックス感染におけるTight junctionタンパク欠損の影響 Invited

    佐藤光, 笠松純, 松本郁美, 石井恵子, 月田早智子, 川上和義

    第3回東北医真菌研究会　2019/12/20

  17. Effect of Claudin-18 deficiency on the host defense to pulmonary infection with Cryptococcus neoformans

    Sato K, Kasamatsu J, Ishii K, Tsukita S, Kawakami K

    第48回日本免疫学会学術集会　2019/12/13

  18. 呼吸器ウイルスと宿主プロテアーゼ依存性ウイルストロピズム Invited

    佐藤 光

    第10回感染制御インテリジェンスネットワーク寄附講座セミナー　2019/12/06

  19. クリプトコックス感染におけるIL-17AによるTh1免疫応答の制御と防御機構への影響

    佐藤光, 笠松純, 山本秀輝, 石井恵子, 川上和義

    第63回日本医真菌学会・学術集会　2019/10/11

  20. クリプトコックス感染におけるIL-17Aによる免疫応答の制御と防御機構への影響

    佐藤光, 笠松純, 山本秀輝, 石井恵子, 川上和義

    第73回日本細菌学会東北支部総会　2019/08/22

  21. クリプトコックス感染におけるIL-17Aを介したTh1免疫応答の制御と防御機構への影響

    佐藤光, 笠松純, 山本秀輝, 石井恵子, 川上和義

    第93回日本感染症学会総会・学術講演会　2019/04/04

  22. インターロイキン17によるクリプトコックス感染免疫応答の制御 Invited

    佐藤光, 笠松純, 山本秀輝, 石井恵子, 川上和義

    第2回東北医真菌研究会　2018/12

  23. Analyses of host serine proteases involved in cleavage of HE protein of the influenza C virus

    Sato K, Hayashi H, Shimotai Y, Matsuzaki Y, Yamaya M, Hongo S, Kawakami K, Nishimura H

    2017/10

  24. C型インフルエンザウイルスHEタンパクの開裂に関わる宿主プロテアーゼの解析

    佐藤光, 林日出喜, 下平義隆, 松嵜葉子, 山谷睦雄, 本郷誠治, 川上和義, 西村秀一

    第71回日本細菌学会東北支部総会　2017/08

  25. ヒトメタニューモウイルスの分離用に新たに見出した培養細胞の有用性の検討

    佐藤光, 渡邊王志, 大宮卓, 千葉ふみ子, 貴田岡節子, 久間木悟, 永井幸夫, 林昌浩, 鈴木民夫, 川上和義, 西村秀一

    第53回宮城県公衆衛生学会学術総会　2017/07

  26. C型インフルエンザウイルスHEタンパクの開裂に関わる宿主プロテアーゼの解析

    佐藤光, 林日出喜, 下平義隆, 山谷睦雄, 本郷誠治, 川上和義, 西村秀一

    第31回インフルエンザ研究者交流の会シンポジウム　2017/06

  27. C-type lectin receptors によるクリプトコックスの認識と感染防御 Invited

    佐藤光, 川上和義

    第60回日本医真菌学会総会・学術集会　2016/10

  28. A Novel Efficient Isolation System of Human Parainflenza and Human Metapneumoviruses That Shows Apparent Cytopathy Using a Cell Line, MNT-1

    Sato K, Watanabe O, Ohmiya S, Chiba F, Hayashi M, Suzuki T, Kawakami K, Nishimura H

    第64回日本ウイルス学会学術集会　2016/10

  29. ヒトパラインフルエンザ及びメタニューモウイルスの分離における新規培養細胞MNT-1の有用性の検討

    佐藤光, 渡邊王志, 大宮卓, 千葉ふみ子, 林昌浩, 鈴木民夫, 川上和義, 西村秀一

    第70回日本細菌学会東北支部総会　2016/08

  30. パラインフルエンザウイルスの分離におけるMNT-1細胞の有用性の検討

    佐藤光, 大宮卓, 西村秀一

    第57回日本臨床ウイルス学会　2016/06

  31. 並行輸入された経鼻インフルエンザ生ワクチン「フルミスト」に含まれるウイルスの感染価の解析

    佐藤光, 菊地佑樹, 真砂佳史, 大宮卓, 伊藤洋子, 大村達夫, 西村秀一

    第30回インフルエンザ研究者交流の会シンポジウム　2016/06

  32. 並行輸入された経鼻インフルエンザ生ワクチン、フルミストに含まれるウイルスの感染価の解析

    佐藤光, 菊地佑樹, 真砂佳史, 大宮卓, 伊藤洋子, 大村達夫, 西村秀一

    第90回日本感染症学会総会・学術講演　2016/04

  33. 並行輸入された経鼻インフルエンザ生ワクチンに含まれるウイルスの感染価の解析

    佐藤光, 菊地佑樹, 真砂佳史, 大宮卓, 伊藤洋子, 大村達夫, 西村秀一

    第19回日本ワクチン学会学術集会　2015/10

  34. 真菌感染におけるⅠ型インターフェロンの産生と感染防御における役割 Invited

    佐藤光, 山本秀輝, 野村俊樹, 石井恵子, 川上和義

    第33回東北免疫研究会　2014/03

  35. Defect of type I interferon receptor leads to improved infection with Cryptococcus neoformans in parallel to increased production of IFN-γ and MUC5AC in lungs

    Sato K, Yamamoto H, Ishii K, Kawakami K

    第42回日本免疫学会学術集会　2013/12

  36. Cryptococcus neoformans 感染免疫応答における1型インターフェロン受容体欠損の影響

    佐藤光, 松村香菜, 石井恵子, 川上和義

    第57回日本医真菌学会総会　2013/09

  37. I型インターフェロン受容体欠損マウスにおけるCryptococcus neoformansの排除とムチン産生の亢進

    佐藤光, 山本秀輝, 石井恵子, 川上和義

    第67回日本細菌学会東北支部総会　2013/08

  38. Cryptococcus neoformans 感染防御におけるtype 1 interferonの役割

    佐藤光, 山本秀輝, 石井恵子, 川上和義

    第24回日本生体防御学会学術総会　2013/07

  39. Immune-adjuvant activity of oligonucleotide DNA from Cryptococcus neoformans

    Sato K, Nakamura Y, Yamamoto H, Matumura K, Ishii K, Kawakami K

    第41回日本免疫学会学術集会　2012/12

  40. クリプトコックス感染初期のIFN-γ産生におけるCARD9 の役割とメモリーフェノタイプT 細胞の関与

    佐藤光, 山本秀輝, 中村優里, 高橋友里恵, 松村香菜, 石井恵子, 原博満, 館正弘, 川上和義

    第66回日本細菌学会東北支部総会　2012/08

  41. CARD9欠損によるクリプトコックス感染の増悪機序

    佐藤光, 山本秀輝, 中村優里, 石井恵子, 松村香菜, 館正弘, 原博満, 川上和義

    第23回日本生体防御学会学術総会　2012/07

Show all Show first 5

Research Projects 21

  1. Intravenous administration of batroxobin enhances wound healing via multifaceted mechanisms derived from a snake venom–based therapeutic approach

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2026/04/01 - 2029/03/31

  2. Development of a novel COVID-19 intranasal vaccine using the adjuvant function of iron oxide nanoparticles

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2025/04/01 - 2028/03/31

  3. Development of Novel Antimicrobial Peptide based on CopW for Antimicrobacterial Resistant Pathogens

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2025/04/01 - 2028/03/31

  4. 酸化鉄ナノ粒子を用いた新規COVID-19ワクチンの開発

    Offer Organization: 武田科学振興財団

    System: ハイリスク新興感染症研究助成

    2022/08 - 2027/05

  5. 粘膜免疫を誘導可能な酸化鉄ナノ粒子を基盤とした新規肺炎球菌多価ワクチンの開発

    佐藤 光, 石井 恵子, 青柳 哲史

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2024/04 - 2027/03

  6. 熱傷治療に新たな選択肢を-感染制御と上皮化誘導を両立するナノ型乳酸菌-

    山口 賢次, 菅野 恵美, 丹野 寛大, 佐藤 光, 工藤 大介, 今井 啓道, 庄司 未樹

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(C)

    Institution: 東北大学

    2023/04/01 - 2026/03/31

    More details Close

    本年度は急性創傷におけるナノ型乳酸菌の効果の検証と熱傷創モデルの確立を中心に研究を進めた。 急性創傷におけるナノ型乳酸菌の効果に関しては、直接投与の濃度を検証し、さらに初回単回投与での創閉鎖率の改善を認めた。加えて、病理学的解析においても、CD31陽性血管数やαSMA陽性筋繊維芽細胞数の増加を認め、創傷治癒に関わる肉芽の増生を認めた。上皮化に関しても、上皮の進展率の上昇を認め、増生した肉芽上に皮膚が進展し、治癒が促進していることを確認できた。 急性期において炎症の調節に必要なサイトカインに関してELISA法での解析を行ったところ、IL-6やTNF-αの早期での上昇を認めた。加えて、好中球の遊走に関与するCXCL2やCXCL1なども著明な上昇を認めた。これらは、乳酸菌を急性創傷に投与することで創部における炎症が惹起され、創傷治癒過程における炎症期のメカニズムと合致する。炎症を惹起することで創の清浄化が促進する可能性が示唆された。さらに、抗炎症に作用するI L-10も後期にて上昇を認めた。炎症期から増殖期への移行を適切にかつ早期に誘導することで、創傷治癒を早めている可能性がある。今後、フローサイトメトリーで創部に遊走される白血球の分画を解明し、創傷治癒過程の変化を観察する予定である。 熱傷創モデルに関しては、マウス背部に電気ごてで作成した熱傷創の治癒過程及び病理学的変化を解析した。熱傷創が治癒する過程と、温度による変化、保護剤による違いなどを検討している。今後、標準的な治癒過程を明らかにし、ナノ型乳酸菌投与による変化を比較検討していく予定である。

  7. 酸化鉄ナノ粒子を基盤とした粘膜免疫誘導型呼吸器感染症ワクチンの開発

    Offer Organization: 日本医療研究開発機構

    System: 「橋渡し研究プログラム」研究開発課題シーズA

    2025/04 - 2026/03

  8. 鼻腔内免疫を誘導可能な新規COVID-19ワクチンの開発

    Offer Organization: 杏の森財団

    System: 令和7年度 杏の森財団研究助成

    2024/11 - 2025/10

  9. 「食べる」を支える、がん治療に伴う粘膜障害に対する新規ケア法の創出

    菅野 恵美, 丹野 寛大, 佐藤 佑樹, 佐藤 光, 庄司 未樹

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2024/04/01 - 2025/03/31

  10. 消化管をケアし、がん治療に伴う栄養障害を改善する革新的技術の創出

    菅野 恵美, 丹野 寛大, 佐藤 佑樹, 佐藤 光, 庄司 未樹

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2023/06/30 - 2025/03/31

  11. 「食べる」を支える、がん治療に伴う粘膜障害に対する新規ケア法の創出

    菅野 恵美, 丹野 寛大, 佐藤 光, 庄司 未樹

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(B)

    Category: 基盤研究(B)

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  12. 新規免疫抑制分子Plet-1の機能解析と革新的なARDS治療薬の開発

    笠松 純, 佐藤 光, 児玉 栄一

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 基盤研究(C)

    Category: 基盤研究(C)

    Institution: 東北大学

    2022/04/01 - 2025/03/31

  13. 飲む褥瘡予防法の確立に向けた、皮膚－腸管ネットワークによる創傷治癒制御機構の解明

    菅野 恵美, 丹野 寛大, 佐藤 光, 高木 尚之

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 挑戦的研究(萌芽)

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2021/07/09 - 2023/03/31

  14. Elucidation of the molecular mechanism of exacerbation of cryptococcal infection by diabetes

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists

    Category: Grant-in-Aid for Early-Career Scientists

    Institution: Tohoku University

    2021/04 - 2023/03

  15. クリプトコックスの潜伏感染・内因性再燃診断のためのIGRA法の開発 Competitive

    佐藤 光

    Offer Organization: 公益財団法人MSD生命科学財団

    System: 研究助成2019 －感染症領域－ 【若手研究】

    2020/01 - 2021/12

  16. 皮膚-肝臓間クロストークによる創傷治癒の制御、糖尿病における制御機構の破綻

    菅野 恵美, 丹野 寛大, 館 正弘, 高木 尚之, 笠松 純, 佐藤 光, 丸山 良子

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 挑戦的研究(萌芽)

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2019/06/28 - 2021/03/31

  17. ハイリスク状態におけるクリプトコックスに対する易感染性の免疫機序の解明 Competitive

    佐藤 光

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業 若手研究

    2019/04 - 2021/03

  18. Fタンパクの開裂領域に蛋白分解酵素フリンによるアミノ酸配列認識パターンを有する3型ヒトパラインフルエンザウイルスの解析 Competitive

    佐藤 光

    Offer Organization: 国立病院機構

    System: 仙台医療センター臨床研究部助成金

    2018/04 - 2019/03

  19. C型インフルエンザウイルスHEタンパクの開裂に関わる宿主プロテアーゼの解析 Competitive

    佐藤 光

    Offer Organization: 国立病院機構

    System: 仙台医療センター臨床研究部助成金

    2017/04 - 2018/03

  20. ヒトメタニューモウイルスの分離用に新たに見出した培養細胞の有用性の検討 Competitive

    佐藤 光

    Offer Organization: 宮城県公衆衛生協会

    System: 宮城県公衆衛生研究振興基金研究助成金

    2016/04 - 2017/03

  21. ヒトメタニューモウイルスの分離用に新たに見出した培養細胞の有用性の検討 Competitive

    佐藤 光

    Offer Organization: 政策医療振興財団

    System: 政策医療振興財団研究助成金

    2016/04 - 2017/03

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Teaching Experience 9

  1. 生体防御学　東北大学医学部保健学科

  2. 基礎ゼミ～臨床検査における生体及び検体情報とは～ (補助)　東北大学

  3. 臨床微生物学実習　東北大学医学部保健学科

  4. 基礎微生物学実習　東北大学医学部保健学科

  5. 新人教育研修 (臨床検査技師)～ウイルス検査について～　国立病院機構 東北ブロック

  6. Topics and Discussions　東北大学大学院医学系研究科

  7. 病原微生物学　東北大学医学部保健学科

  8. 微生物学I　東北大学医学部保健学科

  9. 微生物学II　東北大学医学部保健学科

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Social Activities 11

  1. サイエンス・パートナーシップ・プログラム (SPP)

    2023/07/15 -

  2. サイエンス・パートナーシップ・プログラム (SPP)

    2022/07/09 -

  3. サイエンス・パートナーシップ・プログラム (SPP)

    2021/07/17 -

  4. サイエンス・パートナーシップ・プログラム (SPP)

    2019/05/25 -

  5. 第2回東北医真菌研究会

    2018/12 -

  6. 第17回みちのくウイルス塾

    2018/07 -

  7. 第16回みちのくウイルス塾

    2017/07 -

  8. 第15回みちのくウイルス塾

    2016/07 -

  9. 第14回みちのくウイルス塾

    2015/07 -

  10. 第68回日本細菌学会東北支部総会

    2014/08 -

  11. 第13回みちのくウイルス塾

    2014/07 -

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