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Role of mucosal tissue microbiota in neurotropic virus infection

Research Project

Project/Area Number 18H02857
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 54030:Infectious disease medicine-related
Research InstitutionNational Institutes of Biomedical Innovation, Health and Nutrition

Principal Investigator

IIJIMA NORIFUMI  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 細胞核輸送ダイナミクスプロジェクト, サブプロジェクトリーダー (40612552)

Co-Investigator(Kenkyū-buntansha) 戸田 知得  北海道大学, 獣医学研究院, 助教 (70571199)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
KeywordsB 細胞応答 / 組織局在型メモリー T 細胞 / 粘膜感染 / 末梢組織免疫応答 / 微生物叢
Outline of Final Research Achievements

Herpes simplex virus (HSV), one of the neurotropic viruses, is impossible to cure latently infected nerve tissue because there is currently no vaccine that can prevent infection. Therefore, we aimed to establish a new treatment method by clarifying the importance and limitations of the defense mechanisms that are constructed in mucosal tissues, the site of HSV infection. In this study, we analyzed the details of the unresolved mechanism by which tissue-localized memory T cells (TRMs) accumulating in the mucosa completely inhibit the retrograde transport of HSV from the mucosa to the nerves.

Academic Significance and Societal Importance of the Research Achievements

性感染症を発症する病原体として知られている単純ヘルペスウイルス2型 (HSV-2) は、生殖器の粘膜から感染し、神経組織へと移行する神経向性ウイルスである。HSVー2 感染を防御するワクチン開発の研究が進められているが、現在も HSV-2 感染を防御できる方法は全くない。それ故、一度神経組織に侵入したウイルスを除去できないため、HSV-2 感染部位における生体防御機構の詳細を明らかにすることにより、新たな治療標的を同定することができる可能性が高い。それ故、申請者は生殖粘膜組織に集積する免疫細胞群や常在微生物群の役割に着目し、粘膜組織に構築される生体防御機構の詳細を明らかにした。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (27 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 8 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 8 results) Book (4 results)

  • [Int'l Joint Research] Yale University School of Medicine/Harvard Medical School/Geisel School of Medicine at Dartmouth(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Yale University School of Medicine/Harvard Medical School/Geisel School of Medicine at Dartmouth(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Expectation for sweet taste changes peripheral glucose metabolism via basolateral amygdala2022

    • Author(s)
      Izumi Yamamoto, Toya Yonekura, Taiga Ishimoto, Shu-Cheng Xu, Norifumi Iijima, Kazuhiro Kimura, Sabrina Diano, Chitoku Toda
    • Journal Title

      bioRxiv

      Volume: ー Pages: 479066-479066

    • DOI

      10.1101/2022.02.03.479066

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Prostaglandin in the ventromedial hypothalamus regulates peripheral glucose metabolism2021

    • Author(s)
      LeeML, Matsunaga H, Sugiura Y, Hayasaka T, Yamamoto I, Imoto D, SuematsuM, Iijima N, Kimura K, Diano S, Toda C.
    • Journal Title

      Nature Communications

      Volume: Not determined Issue: 1 Pages: 2330-2330

    • DOI

      10.1038/s41467-021-22431-6

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Refeeding activates neurons in the dorsomedial hypothalamus to inhibit food intake and promote positive valence2021

    • Author(s)
      Daigo Imoto, Izumi Yamamoto, Hirokazu Matsunaga, Toya Yonekura, Ming-Liang Lee, Kan X Kato, Takeshi Yamasaki, Shucheng Xu, Taiga Ishimoto, Satoshi Yamagata, Ken-Ichi Otsuguro, Motohiro Horiuchi , Norifumi Iijima, Kazuhiro Kimura, Chitoku Toda
    • Journal Title

      Molecular Metabiolism

      Volume: 54 Pages: 101366-101366

    • DOI

      10.1016/j.molmet.2021.101366

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Memory Lymphocyte Clusters in Genital Immunity: Role of Tissue-Resident Memory T Cells (TRM).2020

    • Author(s)
      Iijima N
    • Journal Title

      Current Topics in Microbiology and Immunology

      Volume: 426 Pages: 83-117

    • DOI

      10.1007/82_2020_213

    • ISBN
      9783030517465, 9783030517472
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of prodynorphin neurons in the dorsomedial hypothalamus inhibits food intake and promotes positive valence2020

    • Author(s)
      Imoto D, Yamamoto I, Matsunaga H, Yonekura T, Lee ML, Kato KX, Yamasaki T, Otsuguro K, Horiuchi M, Iijima N, Kimura K, Toda C.
    • Journal Title

      bioRxiv

      Volume: 0 Pages: 1-17

    • DOI

      10.1101/2020.07.02.183780

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] Prostaglandin in the ventromedial hypothalamus regulates peripheral glucose metabolism2020

    • Author(s)
      LeeML, Matsunaga H, Sugiura Y, Hayasaka T, Yamamoto I, Imoto D, SuematsuM, Iijima N, Kimura K, Diano S, Toda C.
    • Journal Title

      bioRxiv

      Volume: 0 Pages: 1-40

    • DOI

      10.1101/2020.05.18.056374

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] Rapid quantification of NETs in vitro and in whole blood samples by imaging flow cytometry2019

    • Author(s)
      Lelliott PM, Momota M, Lee MSJ, Kuroda E, Iijima N, Ishii KJ, Coban C.
    • Journal Title

      Cytometry A

      Volume: .. Issue: 5 Pages: 565-578

    • DOI

      10.1002/cyto.a.23767

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Migrant memory B cells secrete luminal antibody in the vagina.2019

    • Author(s)
      2)Oh JE*, Iijima N*, Song E, Lu P, Klein J, Jiang R, Kleinstein SH, Iwasaki A (* equally contributed).
    • Journal Title

      Nature

      Volume: 571 Issue: 7763 Pages: 122-126

    • DOI

      10.1038/s41586-019-1285-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection.2019

    • Author(s)
      Amezcua Vesely MC, Pallis P, Bielecki P, Low JS, Zhao J, Harman CCD, Kroehling L, Jackson R, Bailis W, Licona-Limon P, Xu H, Iijima N, Pillai PS, Kaplan DH, Weaver CT, Kluger Y, Kowalczyk MS, Iwasaki A, Pereira JP, Esplugues E, Gagliani N, Flavell RA.
    • Journal Title

      Cell

      Volume: 178 Issue: 5 Pages: 1176-1188

    • DOI

      10.1016/j.cell.2019.07.032

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 粘膜ウィルス感染に対する末梢組織生体防御機構の解明に取り組んで2019

    • Author(s)
      飯島則文
    • Journal Title

      The Japanese Journal of Antibiotics

      Volume: 72 Pages: 25-30

    • NAID

      40021853607

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Immunological association of inducible bronchus-associated lymphoid tissue organogenesis in Ag85B-rHPIV2 vaccine-induced anti-tuberculosis mucosal immune responses in mice.2018

    • Author(s)
      Nagatake T, Suzuki H, Hirata S, Matsumoto N, Wada Y, Morimoto S, Nasu A, Shimojou M, Kawano M, Ogami K, Tsujimura Y, Kuroda E, Iijima N, Hosomi K, Ishii KJ, Nosaka T, Yasutomi Y, Kunisawa J.
    • Journal Title

      Int Immunol

      Volume: 30 Issue: 10 Pages: 471-481

    • DOI

      10.1093/intimm/dxy046

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 末梢組織に構築される生体防御機構の重要性2022

    • Author(s)
      飯島 則文
    • Organizer
      東京大学医科学研究所、国際共同利用・共同研究拠点2021年度国際共同利用・共同研究拠点成果報告会(千葉大学真菌医学研究センターとの合同開催)
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Invited
  • [Presentation] 生体に寄生する” 病原体が引き起こす様々な慢性疾患発症の予防・治療薬開発戦略2021

    • Author(s)
      飯島 則文
    • Organizer
      戦略的創造研究推進事業(新技術シーズ創出)令和3年度戦略目標及び革新的先端研究開発支援事業令和3年度研究開発目標の検討に関するワークショップ(感染症創薬学の新潮流)
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Neuro-Immune Control of Mucosal Virus Infection2021

    • Author(s)
      Norifumi IIJIMA
    • Organizer
      THE UEHARA INTERNATIONAL SYMPOSIUM 2021 brain-periphery interactions - an increasingly significant area in life sciences and medicine 上原国際シンポジウム
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Presentation] 神経および末梢組織における生体防御機構の重要性2021

    • Author(s)
      飯島 則文
    • Organizer
      日本神経免疫学会 第9回神経と免疫を語る会
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Invited
  • [Presentation] 生体に寄生する” 病原体が引き起こす様々な慢性疾患発症の予防・治療薬開発戦略2020

    • Author(s)
      飯島 則文
    • Organizer
      戦略的創造研究推進事業(新技術シーズ創出)令和3年度戦略目標及び革新的先端研究開発支援事業令和3年度研究開発目標の検討に関するワークショップ(感染症創薬学の新潮流)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 生殖器粘膜ウィルス感染に対する末梢組織免疫制御機構の解明2019

    • Author(s)
      飯島則文
    • Organizer
      第 92 回 日本細菌学会総会 シンポジウム3 生体フロントラインバリアの破綻と感染症
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Invited
  • [Presentation] Migrant memory B cells secrete luminal antibody in the vagina2019

    • Author(s)
      Norifumi Iijima
    • Organizer
      The 18th Awaji International Forum on Infection and Immunity 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 組織局在型メモリー T 細胞に着目した潜伏感染ウィルスの再活性化機構の解明2019

    • Author(s)
      飯島則文
    • Organizer
      J-PRIDE 研究成果発表会 重症・難治性感染症の理解と予防・治療法の開発に向けて~若手研究者たちの挑戦~
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Peripheral immune control of latent virus infection2019

    • Author(s)
      Norifumi Iijima
    • Organizer
      大阪大学免疫学フロンティア研究センター IFReC セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 性感染症に対する末梢組織生体制御機構の解明2018

    • Author(s)
      飯島則文
    • Organizer
      第71回日本細菌学会関西支部総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] 「感染・炎症・免疫」 単純ヘルペスウイルス 2 型 (HSV-2) 感染に対する末梢組織免疫記憶メカニズムの仕組み2022

    • Author(s)
      飯島則文
    • Total Pages
      16
    • Publisher
      羊土社
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Book] 実験医学別冊 『新世代フローサイトメトリー活用スタンダード 生物学・医学・創薬研究で定量・多色解析を活かす!基本原理の理解と実践プロトコール』 第二章 II 基礎科学研究・細胞外 6 末梢組織に局在するさまざまな免疫担当細胞の表現型及び機能解析2022

    • Author(s)
      飯島則文
    • Total Pages
      18
    • Publisher
      羊土社
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Book] The Japanese Journal of Antibiotics 粘膜ウィルス感染に対する末梢組織生体防御機構の解明に取り組んで2019

    • Author(s)
      飯島則文
    • Total Pages
      6
    • Publisher
      公益財団法人 日本感染症医薬品協会
    • Related Report
      2018 Annual Research Report
  • [Book] アレルギー・免疫 内因性アジュバントと自己免疫疾患2018

    • Author(s)
      飯島則文 石井健
    • Total Pages
      8
    • Publisher
      医薬ジャーナル社
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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