Cutting edge: Bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression

Flagellin, the structural component of bacterial flagella, is secreted by p athogenic and commensal bacteria. Flagellin activates proinflammatory gene expression in intestinal epithelia. However, only flagellin that contacts b asolateral epithelial surfaces is proinflammatory; apical flagellin has no effect. Pathogenic Salmonella, but not commensal Escherichia coli, transloc ate flagellin across epithelia, thus activating epithelial proinflammatory gene expression. Investigating how epithelia detect flagellin revealed that cell surface expression of Toll-like receptor 5 (TLR5) conferred NF-kappaB gene expression in response to flagellin. The response depended on both ex tracellular leucine-rich repeats and intracellular Toll/IL-1R homology regi on of TLR5 as well as the adaptor protein MyD88. Furthermore, immunolocaliz ation and cell surface-selective biotinylation revealed that TLR5 is expres sed exclusively on the basolateral surface of intestinal epithelia, thus pr oviding a molecular basis for the polarity of this innate immune response. Thus, detection of flagellin by basolateral TLR5 mediates epithelial-driven inflammatory responses to Salmonella.