Molecular basis of host-microbe symbiosis within tissue resident macrophages

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K10088
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: Hiroshima 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
• Keywords: host microbe symbiosis / mucosal immunology / tissue macrophage / interleukin-10 / mitochondrial OCR

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.

Free Research Field

免疫学

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。