TLR4 signaling regulates an inflammatory response to food allergens

Abstract

Abstract Allergies have become increasingly more prevalent over recent years, and this increase has been found to correlate with dysbiosis of the gut microbiota. Bacterial signaling through TLR4 is known to be play a role in allergic sensitization, but the specific host-bacterial interactions and cellular immunological networks have not been elucidated. Preliminary data from our lab has shown that colonization of germ-free mice with feces from a subset of cow’s milk allergic (CMA) infant induces Serum-Amyloid A1 (Saa1) expression in the small intestine epithelium. Saa1 is an acute-phase protein that is part of a transcriptome signature associated with a Th17 response induced by adherent bacteria in the small intestine. Moreover, we show that in mice with a global ablation of TLR4, upregulation of Saa1 in abolished. Because dendritic cells (DCs) are known to be important for mediating intestinal immune responses, we sought to determine the roll of CD11c+ cells in mediating Saa1 upregulation. Antibiotic-treated CD11ccre TLR4fl/fl SPF mice were colonized with CMA feces and intestinal epithelial cells from the ileum were isolated to determine relative expression of Saa1 compared to antibiotic-treated SPF mice. Results from these experiments show that ablation of TLR4 signaling in CD11c+ cells reduces Saa1 upregulation in the ileal epithelium. Future directions of this work include examining immune cell populations in the small intestine draining lymph nodes and lamina propria to determine if this phenotype increases type 3 inflammation to exacerbate an allergic response.