Toll-like receptor signaling regulates mucosal barrier function and antigen acquisition in the small intestine (P3266)

Abstract

Abstract The mucosal immune system must efficiently recognize foreign antigen during intestinal infection and yet avoid triggering inappropriate inflammatory responses to commensal microbes and food antigens. In vivo two-photon imaging revealed that low-molecular weight material can cross the epithelium of the small intestine during goblet cell secretion, a phenomenon termed goblet cell-associated antigen passages (GAPs). GAPs are abundant in the steady-state and selectively deliver foreign antigen to CD103+ lamina propria dendritic cells with tolerogenic potential. However, under pathological conditions, goblet cell secretion and epithelial permeability are dramatically altered. The cellular mechanisms that regulate barrier function in response to luminal microbial products are poorly understood, but have important ramifications for intestinal pathogenesis and oral vaccine efficacy. We found that Toll-like receptor (TLR) ligands introduced acutely into the intestines of germ free mice modulated GAP formation in vivo. Furthermore, mice deficient in TLRs that signal through TRIF, lacked GAPs and had reduced epithelial permeability. We propose that a subset of villus epithelial cells expressing TLR3/TLR4 and containing high levels of serotonin (5HT) can induce GAP formation in the small intestine by secreting 5HT in response to TLR ligands.