TLR5: guardian of the gut

Abstract

The human gastrointestinal tract is a dynamic melting pot of commensal bacteria. Although the apical surface of intestinal epithelial cells lining the gut is constantly exposed to proinflammatory bacterial products, this rarely results in an inflammatory response. By contrast, a recent study by Gewirtz et al.1xCutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. Gewirtz, A.T. et al. J. Immunol. 2001; 167: 1882–1885PubMedSee all References1 has demonstrated that exposure of the basolateral surface (but not the apical side) of intestinal epithelial cells to bacterial flagellin results in substantial upregulation of cellular nuclear factor (NF)-κB gene expression and chemotactic interleukin (IL)-8 production.Further analysis revealed that Toll-like receptor 5 (TLR5) is only expressed on the basolateral, but not apical, surface of model intestinal epithelium. Flagellin-mediated activation of NF-κB was dependent both upon the extracellular leucine-rich repeats and on the intracellular Toll/IL-1 receptor homology region of TLR5, which transmits its signals through the MyD88 adaptor protein.This indicates a mechanism by which the innate immune response of the host is triggered through TLR5 only in the event that gut-associated bacteria (or bacterial products) invade the interior of the host by crossing over to the basolateral surface of the epithelial cell barrier of the gastrointestinal tract. Such an early defense system is likely to induce rapid recruitment of inflammatory cells, helping to prevent systemic infection from occurring.