CRTAM Shapes the Gut Microbiota and Enhances the Severity of Infection

Abstract

Gut lymphocytes and the microbiota establish a reciprocal relationship that impacts the host immune response. Class I-restricted T cell-associated molecule (CRTAM) is a cell adhesion molecule expressed by intraepithelial T cells and is required for their retention in the gut. In this study, we show that CRTAM expression affects gut microbiota composition under homeostatic conditions. Moreover, <i>Crtam^-/-</i> mice infected with the intestinal pathogen <i>Salmonella</i> exhibit reduced Th17 responses, lower levels of inflammation, and reduced <i>Salmonella</i> burden, which is accompanied by expansion of other microbial taxa. Thus, CRTAM enhances susceptibility to <i>Salmonella</i>, likely by promoting the inflammatory response that promotes the pathogen's growth. We also found that the gut microbiota from wild-type mice, but not from <i>Crtam^-/-</i> mice, induces CRTAM expression and Th17 responses in ex-germ-free mice during <i>Salmonella</i> infection. Our study demonstrates a reciprocal relationship between CRTAM expression and the gut microbiota, which ultimately impacts the host response to enteric pathogens.