2022 Fiscal Year Annual Research Report
微生物・細胞内共生現象の解明とその破綻に起因する日和見感染発症機構の解析
Project/Area Number |
19K10088
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Research Institution | Hiroshima University |
Principal Investigator |
高橋 一郎 広島大学, 医系科学研究科(歯), 教授 (20206791)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | 微生物・細胞内共生 / tissue macrophage / S. maltophilia / smlt2713 / perforin-2 / immune metabolism |
Outline of Annual 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, for example commensal bacteria survive within dendritic cells in Peyer’s patches and enhance mucosal IgA responses. 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. Furthermore, bulk RNA sequence analysis clearly exhibited that the symbiotic factor smlt2713 exposed bone marrow derived macrophages predominantly expressed anti-inflammatory genes such as the the acod-1, the arg-1/arg-2, and the lipocalin-2. In vivo, pre-transfer of smlt2713-transduced BMDMs protects against chronic enterocolitis. We thus identify a novel symbiotic network between commensal bacteria and colonic macrophages.
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