Flagellin/TLR5 signalling activates renal collecting duct cells and facilitates invasion and cellular translocation of uropathogenic Escherichia coli.
Uropathogenic Escherichia 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 HT7ΔfliC 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.
Centre de Recherche sur l'Inflammation (CRI), UMRS 1149, Université Denis Diderot - Paris 7, Paris, France; Groupe ATIP-AVENIR INSERM, Université Denis Diderot - Paris 7, Paris, France.
Marcelle
M
Bens
Sophie
S
Vimont
Sanae
S
Ben Mkaddem
Cécilia
C
Chassin
Jean-Michel
JM
Goujon
Viviane
V
Balloy
Michel
M
Chignard
Catherine
C
Werts
Alain
A
Vandewalle
D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D058491:Bacterial Load / Q000276:immunology; D054360:Chemokine CXCL1 / Q000096:biosynthesis; D054426:Chemokine CXCL2 / Q000096:biosynthesis; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005408:Flagellin / Q000276:immunology*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011704:Pyelonephritis / Q000276:immunology / Q000382:microbiology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000276:immunology*; D001743:Urinary Bladder / Q000276:immunology / Q000378:metabolism; D014552:Urinary Tract Infections / Q000276:immunology / Q000382:microbiology; D056689:Uropathogenic Escherichia coli / Q000276:immunology / Q000472:pathogenicity*
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D005408:Flagellin