title: TLR4-initiated and cAMP-mediated abrogation of bacterial invasion of the bladder.
abstract: The remarkable resistance of the urinary tract to infection has been attributed to its physical properties and the innate immune responses triggered by pattern recognition receptors lining the tract. We report a distinct TLR4 mediated mechanism in bladder epithelial cells (BECs) that abrogates bacterial invasion, a necessary step for successful infection. Compared to controls, uropathogenic type 1 fimbriated Escherichia coli and Klebsiella pneumoniae invaded BECs of TLR4 mutant mice in 10-fold or greater numbers. TLR4 mediated suppression of bacterial invasion was linked to increased intracellular cAMP levels which negatively impacted Rac-1 mediated mobilization of the cytoskeleton. Artificially increasing intracellular cAMP levels in BECs of TLR4 mutant mice restored resistance to type 1 fimbriated bacterial invasion. This finding reveals a novel function for TLR4 and another facet of bladder innate defense.
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Jeongmin
authors: J
authors: Song
authors: Brian L
authors: BL
authors: Bishop
authors: Guojie
authors: G
authors: Li
authors: Matthew J
authors: MJ
authors: Duncan
authors: Soman N
authors: SN
authors: Abraham
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000517:prevention & control*; D000242:Cyclic AMP / Q000502:physiology*; D004926:Escherichia coli / Q000472:pathogenicity; D016905:Gram-Negative Bacterial Infections / Q000517:prevention & control; D006801:Humans; D007711:Klebsiella pneumoniae / Q000472:pathogenicity; D051379:Mice; D008809:Mice, Inbred C3H; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D001743:Urinary Bladder / Q000382:microbiology* / Q000502:physiology*; D001745:Urinary Bladder Diseases / Q000517:prevention & control*; D014552:Urinary Tract Infections / Q000517:prevention & control*; D019459:Urothelium / Q000382:microbiology
chemical_list: C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000242:Cyclic AMP
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