GSE124848
Directed endocytosis mediates immune communication between an epithelial commensal microbe and the host
Commensal bacteria influence host physiology, including immune responses, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB), which are immunomodulatory commensal microbes, are transferred into intestinal epithelial cells by adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. SFB transfer microbial cell wall-associated proteins, including an antigen that stimulates mucosal Th17 cell differentiation, into the cytosol of epithelial cells. Removal of CDC42 activity in vivo led to disruption of endocytosis induced by SFB, decreased epithelial antigen acquisition with consequent loss of immune modulation by SFB-specific CD4 T cells and mucosal Th17 cells.  Our findings indicate direct communication between a resident gut microbe and the host and show that intestinal epithelial cells acquire antigens from commensal bacteria for generation of T-cell responses to the resident microbiota. Overall design: Intestinal epithelial cells from WT and IEC?CDC42 mice were isolated to performed RNAseq.