Escherichia coli colonization restores mucosal immune tone during antibiotic treatment (MUC5P.759)

Abstract

Molecules derived from gut-colonizing microbes contribute to intestinal homeostasis by stimulating innate immune receptors and maintaining a basal level of activation of host antimicrobial defenses. Depletion of intestinal microbes by treatment with antibiotics severely dampens these responses, increasing the risk for colonization and infection with pathogenic bacteria. A major consequence of antibiotic treatment is downregulation of the antimicrobial protein RegIII-γ. RegIII-γ expression is markedly decreased during antibiotic treatment but can be induced by administration of Toll-like receptor (TLR) ligands derived from Gram-negative bacteria. This observation suggests a role for Gram-negative organisms in stimulating RegIII-γ intestinal levels. In this study, we investigated the ability of several E. coli and K. pneumoniae strains to induce RegIII-γ in the mouse intestine during antibiotic stress. We find that although both bacterial species colonize the gastrointestinal tract of antibiotic-treated mice, only E. coli restores RegIII-γ expression in the ileum. E. coli, but not K. pneumoniae, induces IL-22 expression, a requisite step for RegIII-γ, induction, in the small intestinal lamina propria. Flagellin and TLR5 signaling are not required for E.coli-mediated RegIII-γ induction. Our findings suggest that Gram-negative bacteria colonizing the intestine differ in their ability to mediate IL-22-dependent RegIII-γ.