Campylobacter jejuni disrupts polarized TLR9 signaling in colonic epithelial cells

Abstract

Campylobacter jejuni infection is associated with an increased risk of developing inflammatory bowel disease (IBD) via mechanisms that remain obscure. TLR9 signaling in response to bacterial DNA is essential to intestinal homeostasis, possibly by regulating the T helper (Th) 17‐cell line. IL‐25 is a known inhibitor of the proinflammatory Th17 pathway.AimTo assess whether C. jejuni contributes to the development of IBD by disrupting TLR9 signaling using a human colonic (T84) cell line and a DSS model of colitis.ResultsApical application of a TLR9 agonist (ISS‐ODN, 5μg/mL) elicited a significant increase in transepithelial resistance across control T84 monolayers, indicating a tightening of the epithelial barrier. This response was lost in C. jejuni‐infected monolayers. Infected cells secreted significantly more IL‐8 in response to a basolaterally applied TLR9 agonist when compared to control cells. Real‐time PCR revealed a greater than 2 fold increase in TLR9 expression in human colonic biopsies exposed to C.jejuni. C57Bl/6 mice inoculated with 1 × 108 C.jejuni demonstrated an increase in occult blood score and a significant reduction in colonic IL‐25 levels following treatment with DSS compared to mice treated with C. jejuni or DSS alone.ConclusionsC. jejuni may increase the risk of developing IBD by disrupting epithelial TLR9 signaling and reducing IL‐25 levels. Funded by CAG‐CIHR‐CCFC.