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Cutting Edge |


*
Epithelial Pathobiology Division, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322; and
Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080
Flagellin, the structural component of bacterial flagella, is
secreted by pathogenic and commensal bacteria. Flagellin activates
proinflammatory gene expression in intestinal epithelia. However, only
flagellin that contacts basolateral epithelial surfaces is
proinflammatory; apical flagellin has no effect. Pathogenic
Salmonella, but not commensal Escherichia
coli, translocate 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-
B gene expression in response to
flagellin. The response depended on both extracellular leucine-rich
repeats and intracellular Toll/IL-1R homology region of TLR5 as well as
the adaptor protein MyD88. Furthermore, immunolocalization and cell
surface-selective biotinylation revealed that TLR5 is expressed
exclusively on the basolateral surface of intestinal epithelia, thus
providing 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.
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