Critical Role for a Subset of Intestinal Macrophages in Shaping Gut Microbiota in Adult Zebrafish

Abstract

Summary: 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. : Whether intestinal macrophages shape adult gut microbiota has not been demonstrated. Shiau et al. show that a severe loss of intestinal macrophages in adult zebrafish irf8 mutants can cause destabilization of gut commensal microbiota and a reduction of C1q expressions. Macrophage-specific rescue of irf8 mutants can reverse these effects. Keywords: intestinal macrophages, microbiota, complement, interferon regulatory factor, irf8, c1q, microglia, zebrafish