| 研究実績の概要 |
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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