Innate Immune Responses to Commensal Bacteria in the Gut Epithelium

Abstract

SESSION III INNATE IMMUNE RESPONSES TO COMMENSAL BACTERIA IN THE GUT EPITHELIUM Shipra Vaishnava, Cassie L. Behrendt, and Lora V. Hooper, University of Texas Southwestern Medical Center at Dallas, USA The authors report no conflicts of interest. The mammalian gut harbors a coevolved microbial consortium that makes critical contributions to host health. Despite the enormous number of bacteria in the luminal compartment, microbial penetration of mucosal surfaces is relatively rare. We have shown that microbial colonization of germ-free mice triggers epithelial expression of RegIII-γ, a secreted C-type lectin. RegIII-γ binds intestinal bacteria but lacks the complement recruitment domains present in other microbe-binding mammalian C-type lectins. We have demonstrated that RegIII-γ and its human counterpart—hepatocarcinoma-intestine-pancreas/pancreatic-associated protein—are directly antimicrobial proteins that bind their bacterial targets via interactions with peptidoglycan carbohydrate. We propose that these proteins represent an evolutionarily primitive form of lectin-mediated innate immunity, and that they reveal intestinal strategies for maintaining symbiotic host–microbial relations. Analysis of the host factors that regulate RegIII-γ expression has uncovered a mechanism of epithelial cell–intrinsic sensing of intestinal bacteria in vivo. We have shown that Paneth cells, specialized secretory epithelia of the small intestine, detect bacteria via cell-intrinsic MyD88-depende…