Open AccessSalmonella typhimuriumtranscytoses flagellin via an SPI2-mediated vesicular transport pathway
Author(s) -
Sean Lyons,
Lixin Wang,
James E. Casanova,
Shanthi V. Sitaraman,
Didier Merlin,
Andrew T. Gewirtz
Publication year - 2004
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.01500
Subject(s) - flagellin , transcytosis , biology , tlr5 , microbiology and biotechnology , flagellum , secretion , vesicle , endocytosis , bacteria , signal transduction , receptor , biochemistry , tlr2 , tlr4 , genetics , membrane
Apical colonization of polarized epithelia by Salmonella typhimurium results in translocation of flagellin to the basolateral membrane domain, thus enabling activation of toll-like receptor 5 (TLR5)-mediated pro-inflammatory gene expression. Such flagellin transcytosis occurred without a change in epithelial permeability to 40 kDa FITC dextran, did not require bacterial motility and was independent of transepithelial movement of intact bacteria. Flagellin transcytosis was blocked at 20°C, suggesting dependence on vesicular transport consistent with results from confocal microscopy that showed flagellin independent of bacteria inside epithelial cells. Furthermore, vesicles isolated from S. typhimurium-infected epithelia were highly enriched in flagellin. Flagellin transcytosis was dependent upon genes of Salmonella pathogenicity island (SPI)-2, which alter vesicular trafficking, but independent of SPI-1 that mediates bacterial invasion. Furthermore, such SPI-2 mutants were unable to mediate the localization of flagellin into intracellular vesicles consistent with flagellin transcytosis mediated by a S. typhimurium take-over of host vesicle trafficking pathways. As a result of their inability to transcytose flagellin, apical colonization by SPI-2 mutants induced substantially less epithelial IL-8 secretion than wild-type strains suggesting that such SPI-2 mediated transcytosis of flagellin plays a role in the pathogenesis of the mucosal inflammation characteristic of human Salmonellosis.