Uropathogenic Escherichia coli dominantly suppress the innate immune response of bladder epithelial cells by a lipopolysaccharide- and Toll-like receptor 4-independent pathway.
Urinary tract infections are a major source of morbidity among women, with the majority caused by uropathogenic Escherichia coli. Our objective was to test if uropathogenic E. coli suppress the innate immune response of bladder epithelial cells. We found that bladder epithelial cells secrete interleukin-6 and interleukin-8 in response to non-pathogenic E. coli, whereas they failed to do so in response to uropathogenic E. coli. Uropathogenic E. coli prevented interleukin-6 secretion in response to non-pathogenic E. coli and a panel of Toll-like receptor agonists, as well as to interleukin-1beta, but not to tumor necrosis factor alpha. These results indicate that receptors with a Toll/interleukin-1 receptor domain are specifically targeted, and that suppression is not a consequence of toxicity. One candidate for mediating immune suppression is bacterial lipopolysaccharide. However, lipopolysaccharide isolated from either uropathogenic or non-pathogenic E. coli stimulated interleukin-6 secretion to similar levels. In addition, uropathogenic E. coli did not stimulate interleukin-6 secretion from cells expressing a dominant negative Toll-like receptor 4, and prevented cells lacking Toll-like receptor 4 from secreting interleukin-6 in response to synthetic lipoprotein. We conclude that uropathogenic E. coli suppress the innate immune response through a pathway partially independent of lipopolysaccharide and Toll-like receptor 4.
Hilbert
David W
DW
Research and Development Department, Medical Diagnostic Laboratories LLC, 2439 Kuser Rd., Hamilton, NJ 08690, USA.
Pascal
Kristen E
KE
Libby
Erika K
EK
Mordechai
Eli
E
Adelson
Martin E
ME
Trama
Jason P
JP
D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology*; D004926:Escherichia coli / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D001743:Urinary Bladder / Q000276:immunology*
D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha