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Molecular basis of host-microbe symbiosis within tissue resident macrophages

Research Project

Project/Area Number 19K10088
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionHiroshima University

Principal Investigator

takahashi ichiro  広島大学, 医系科学研究科(歯), 教授 (20206791)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordshost microbe symbiosis / mucosal immunology / tissue macrophage / interleukin-10 / mitochondrial OCR / 微生物・細胞内共生 / S. maltophilia / smlt2713 / perforin-2 / immune metabolism / macrophage / IL-10 / 粘膜免疫 / マクロファージ / 自然炎症 / 微生物細胞内共生 / ミトコンドリア / 炎症制御 / 恒常性
Outline of Research at the Start

日和見感染重症化の背景にある個体を取り巻く環境因子(食餌・抗生物質・内因性侵害物質など)によって誘発される宿主・微生物間相互作用の異常とそれに起因する宿主免疫系の破綻機構を解明することは喫緊の課題である。申請者は微生物ゲノム解析を取り入れた粘膜免疫学的研究を通じて、これまで日和見感染原因細菌Stenotrophomonas maltophiliaが健常なマウスの大腸常在マクロファージ内に共生し、定常状態における大腸粘膜の組織恒常性に寄与していることを見出した。本研究では大腸粘膜マクロファージ内へのS. maltophilia共生的持続感染の分子基盤とそれに潜む病原性顕在化の機構解明に取り組む。

Outline of Final Research Achievements

Interactions between the microbiota and the mucosal immune system are absolutely important in shaping mucosal immune responses. It is becoming clear that specific microbes influence specific lymphoid and non-lymphoid populations. We showed that Stenotrophomonas maltophilia is constitutively present in vivo in colonic lamina propria macrophages but not in lymphoid-tissue resident macrophages. Clinically isolated S. maltophilia enter bone marrow-derived macrophages (BMDMs) in vitro and persistent colonization increases mitochondrial respiration and IL-10 production. Colonization by S. maltophilia is impaired by IL-10 deficiency. The bacteria secrete a 25-KDa protein encoded by smlt2713. Expression of smlt2713 in BMDMs induces IL-10 production. Bacteria deficient in smlt2713 show reduced colonization and IL-10 production. We thus identify a novel symbiotic network between commensal bacteria and colonic macrophages.

Academic Significance and Societal Importance of the Research Achievements

微生物細胞内共生という独自の視点から、宿主と微生物の間で繰り広げられている感染現象を理解し、共生関係構築の端緒となる微生物側因子とその宿主作用点を明らかにし、当該生体分子を起点として発動される免疫応答の全貌を解明することは、Covid-19に代表される新興感染症重症化の分子基盤解明につながり、その成果は創薬として人類社会に新たな福音をもたらすことが期待される。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (3 results)

All 2022 2019

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 2 results)

  • [Journal Article] Oral administration of bovine lactoferrin suppresses the progression of rheumatoid arthritis in an SKG mouse model2022

    • Author(s)
      Yanagisawa, A., K. Nagasaki, I. Takahashi, M. Miyauchi, T. Takata, et al.
    • Journal Title

      PLOS ONE

      Volume: 17 (2) Issue: 2 Pages: e0263254-e0263254

    • DOI

      10.1371/journal.pone.0263254

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Persistent colonization of non-lymphoid tissue-resident macrophages by Stenotrophomonas maltophilia2019

    • Author(s)
      Takahashi Ichiro, Hosomi Koji, Nagatake Takahiro, Tobou Hirokazu, Yamamoto Daiki, Hayashi Ikue, Kurashima Yosuke, Sato Shintaro, Shibata Naoko, Goto Yoshiyuki, Maruyama Fumito, Nakagawa Ichiro, Kuwae Asaomi, Abe Akio, Kunisawa Jun, Kiyono Hiroshi
    • Journal Title

      International Immunology

      Volume: 32 Issue: 2 Pages: 133-141

    • DOI

      10.1093/intimm/dxz071

    • NAID

      120006888456

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of hypoxia-associated dendritic cells in colitic mice and effects of probiotics on IL-10 production in inflammatory dendritic-cells under hypoxia2019

    • Author(s)
      Ogita T, Miyamoto J, Hirabayashi Y, Rossi M, Mazzarella G, Takahashi I, Tanabe S, Suzuki T.
    • Journal Title

      Beneficial Microbes

      Volume: 10 Issue: 7 Pages: 801-810

    • DOI

      10.3920/bm2018.0171

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research

URL: 

Published: 2019-04-18   Modified: 2024-01-30  

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