Flagellin/ TLR 5 signalling activates renal collecting duct cells and facilitates invasion and cellular translocation of uropathogenic E scherichia coli

Summary Uropathogenic E scherichia coli ( UPEC ) colonizing kidneys is the main cause of acute pyelonephritis. TLR 5 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 TLR 5 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 CXCL 1 and CXCL 2, and subsequent migration capacity of neutrophils in cultured wild‐type ( WT ) and Tlr4 −/− MCD s, but not in Tlr5 −/− MCD s. UPEC can translocate across intact MCD layers without altering tight junctions. Strikingly, the invasion capacity and transcellular translocation of the UPEC strain HT 7 were significantly lower in Tlr5 −/− than in WT MCD s. The non‐motile HT 7Δ fliC mutant lacking flagellin also exhibited much lower translocation capacities than the HT 7 isolates. Finally, Tlr5 −/− kidneys exhibited less infiltrating neutrophils than WT kidneys one day after the transurethral inoculation of HT 7, and greater delayed renal bacterial loads in the day 4 post‐infected Tlr5 −/− kidneys. Overall, these findings indicate that the epithelial TLR 5 participates to renal antibacterial defence, but paradoxically favours the translocation of UPEC across intact MCD cell layers.