Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Cell Rep. 2018 Oct 9;25(2):424-436. doi: 10.1016/j.celrep.2018.09.025.
The gut microbiota is strongly influenced by environmental factors, although host contribution is far less understood. We leveraged macrophage-deficient interferon regulatory factor irf8 zebrafish mutants to investigate the role of macrophages in this process. In conventionally raised adult irf8-deficient mutants, we found a significant loss of intestinal macrophages associated with a strikingly altered gut microbiota when compared to co-housed siblings. The destabilization of the gut commensal microbiota was associated with a severe reduction in complement C1q genes and outgrowth of a rare bacterial species. Consistent with a critical function of irf8 in adult intestinal macrophages, irf8 is abundantly expressed in these cells normally, and restoring macrophage irf8 expression in irf8 mutants was sufficient to recover commensal microbes and C1q genes expression. This study reports an important subpopulation of intestinal macrophages that requires irf8 to establish in the gut, ensure normal colonization of gut microbes, and prevent immune dysregulation.
肠道微生物群受环境因素的强烈影响，尽管宿主的贡献还远未被理解。我们利用巨噬细胞缺陷型干扰素调节因子 irf8 斑马鱼突变体来研究巨噬细胞在这一过程中的作用。在常规饲养的成年 irf8 缺陷型突变体中，与同笼饲养的兄弟姐妹相比，我们发现肠道巨噬细胞明显减少，肠道微生物群发生了惊人的改变。肠道共生菌群的不稳定与补体 C1q 基因的严重减少和一种罕见细菌物种的生长有关。与 irf8 在成年肠道巨噬细胞中的关键功能一致，irf8 在这些细胞中正常大量表达，在 irf8 突变体中恢复巨噬细胞 irf8 的表达足以恢复共生微生物和 C1q 基因的表达。本研究报告了肠道巨噬细胞的一个重要亚群，该亚群需要 irf8 才能在肠道中建立，确保肠道微生物的正常定植，并防止免疫失调。
