TLR4 facilitates translocation of bacteria across renal collecting duct cells
| Autor: | Guillaume Arlet, Marcelle Bens, Sophie Vimont, Alain Vandewalle, Alexandre Hertig, Béatrice Fernandez, Eric Rondeau, Jean-Michel Goujon, Françoise Cluzeaud, Cécilia Chassin, Mathias W. Hornef |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Lipopolysaccharides
Caveolin 1 Chromosomal translocation Beta-Cyclodextrins Biology medicine.disease_cause urologic and male genital diseases Transfection Bacterial Adhesion Mice Membrane Microdomains medicine Membrane fluidity Escherichia coli Animals Transcellular Kidney Tubules Collecting RNA Small Interfering Lipid raft Inflammation Tight junction urogenital system beta-Cyclodextrins General Medicine eye diseases Cell biology Toll-Like Receptor 4 Protein Transport Cholesterol Basic Research Biochemistry Nephrology lipids (amino acids peptides and proteins) |
| Zdroj: | Journal of the American Society of Nephrology : JASN. 19(12) |
| ISSN: | 1533-3450 |
| Popis: | Uropathogenic Escherichia coli (UPEC) are the most frequent causes of urinary tract infections and pyelonephritis. Renal medullary collecting duct (MCD) cells are the intrarenal site to which UPEC strains prefer to adhere and initiate an inflammatory response, but the ability of UPEC strains to translocate across impermeant MCD cells has not been demonstrated definitively. Here, several UPEC strains adhered to the apical surface and translocated across confluent murine inner MCD cells grown on filters. UPEC strains expressing cytolytic and vacuolating cytotoxins disrupted the integrity of cell layers, whereas noncytolytic UPEC strains passed through the cell layers without altering tight junctions. Apical-to-basal transcellular translocation was dramatically reduced after extinction of Toll-like receptor 4 (TLR4) and the lipid raft marker caveolin-1 by small interfering RNA. Furthermore, disruption of lipid raft integrity by filipin III and methyl-beta-cyclodextrin significantly reduced both the transcellular translocation of UPEC across murine inner MCD cell layers and the stimulation of proinflammatory mediators. Bacterial translocation was also significantly reduced in primary cultures of TLR4-deficient mouse MCD cells compared with MCD cells from wild-type mice. Benzyl alcohol, an anesthetic that enhances membrane fluidity, favored the recruitment of caveolin-1 in lipid rafts and increased the translocation of UPEC across cultured TLR4-deficient MCD cells. These findings demonstrate that the transcellular translocation of UPEC strains across impermeant layers of MCD cells may occur through lipid rafts via a TLR4-facilitated process. |
| Databáze: | OpenAIRE |
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