Mucosal antimicrobial protection toward enteroaggregative Escherichia coli infection is modulated by dietary tryptophan through an IL17-dependent mechanism (MUC4P.846)

Abstract

Abstract Enteroaggregative E. coli (EAEC) is a predominant extracellular pathogen that causes inflammatory diarrhea in individuals worldwide, especially in persons suffering from malnutrition. We previously reported that protein-energy malnutrition abrogates protective Th17-dependent antimicrobial immunity in a murine model of EAEC infection. However, mechanisms whereby malnutrition enhances host-susceptibility to EAEC colonization remain unreported. This study presents evidence that tryptophan is crucial for antibacterial protection against EAEC infection. Mice fed tryptophan-free diet had reduced antimicrobial peptide production coinciding with significantly high pathogen levels. Likewise, bacterial burden occurred in a dose dependent manner when mice were supplemented with glycly-L-tryptophan dipeptide. Low serum tryptophan directly correlated with hampered gene expression levels of cytokines regulating effector IL-17A responses (e.g. IL-23 and IL-6). Mechanistically, orally administered tryptophan enhanced IL-17A and IL-17C production at the colonic and ileal mucosa facilitating antimicrobial defense and protection against EAEC colonization. IL17a-/- and IL17ra-/- mice receiving nourished diets or tryptophan supplements were unable to recover from disease due to impaired intestinal epithelial barrier function. Thus, our data suggests that tryptophan modulates IL17-dependent antimicrobial responses and is required for preventing EAEC colonization and pathogenic disease.