MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10 deficient mice

Commensal bacterial sensing by Toll-like receptors (TLRs) is critical for maintaining intestinal homeostasis, but can lead to colitis in the absence of IL-10. While TLRs are expressed in multiple cell types in the colon, the cell type(s) responsible for the development of colitis currently unknown. Here, we generated mice that are selectively deficient in MyD88 in various cellular compartments in an IL-10−/ − setting. While epithelial expression of MyD88 was dispensable, MyD88 expression in the mononuclear phagocyte (MNP) compartment was required for colitis development. Specifically, phenotypically distinct populations of colonic MNPs expressed high levels IL-1β, IL-23 and IL-6 and promoted Th17 responses in the absence of IL-10. Thus, gut bacterial sensing through MyD88 in MNPs drives inflammatory bowel disease (IBD) when unopposed by IL-10. Increasing evidence supports the notion that (IBD) results from a dysregulated interaction between the host immune system and its commensal microbiota1. Commensal bacteria are most abundant in the colon and they normally co-exist with the host in a mutually beneficial Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use