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- Title
Flagellin/ TLR5 signalling activates renal collecting duct cells and facilitates invasion and cellular translocation of uropathogenic E scherichia coli.
- Authors
Bens, Marcelle; Vimont, Sophie; Ben Mkaddem, Sanae; Chassin, Cécilia; Goujon, Jean‐Michel; Balloy, Viviane; Chignard, Michel; Werts, Catherine; Vandewalle, Alain
- Abstract
Uropathogenic E scherichia coli ( UPEC) colonizing kidneys is the main cause of acute pyelonephritis. TLR5 that senses flagellin was shown to be highly expressed in the bladder and to participate in host defence against flagellated UPEC, although its role in kidneys still remains elusive. Here we show that TLR5 is expressed in renal medullary collecting duct ( MCD) cells, which represent a preferential site of UPEC adhesion. Flagellin, like lipopolysaccharide, stimulated the production of the chemoattractant chemokines CXCL1 and CXCL2, and subsequent migration capacity of neutrophils in cultured wild-type ( WT) and Tlr4−/− MCDs, but not in Tlr5−/− MCDs. UPEC can translocate across intact MCD layers without altering tight junctions. Strikingly, the invasion capacity and transcellular translocation of the UPEC strain HT7 were significantly lower in Tlr5−/− than in WT MCDs. The non-motile HT7Δ fliC mutant lacking flagellin also exhibited much lower translocation capacities than the HT7 isolates. Finally, Tlr5−/− kidneys exhibited less infiltrating neutrophils than WT kidneys one day after the transurethral inoculation of HT7, and greater delayed renal bacterial loads in the day 4 post-infected Tlr5−/− kidneys. Overall, these findings indicate that the epithelial TLR5 participates to renal antibacterial defence, but paradoxically favours the translocation of UPEC across intact MCD cell layers.
- Subjects
FLAGELLIN; TOLL-like receptors; RENAL collecting tubule; CELLULAR signal transduction; ESCHERICHIA coli; PYELONEPHRITIS; CHROMOSOMAL translocation; NEUTROPHILS
- Publication
Cellular Microbiology, 2014, Vol 16, Issue 10, p1503
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1111/cmi.12306