TLR4-initiated and cAMP-mediated abrogation of bacterial invasion of the bladder.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Song, J; Bishop, BL; Li, G; Duncan, MJ; Abraham, SN

Published Date

  • June 14, 2007

Published In

Volume / Issue

  • 1 / 4

Start / End Page

  • 287 - 298

PubMed ID

  • 17710226

Pubmed Central ID

  • PMC1950120

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2007.05.007


  • eng

Conference Location

  • United States