Suppression of bladder epithelial cytokine responses by uropathogenic Escherichia coli.
Urinary tract infections are most commonly caused by uropathogenic strains of Escherichia coli (UPEC), which invade superficial bladder epithelial cells via a type 1 pilus-dependent mechanism. Inside these epithelial cells, UPEC organisms multiply to high numbers to form intracellular bacterial communities, allowing them to avoid immune detection. Bladder epithelial cells produce interleukin-6 (IL-6) and IL-8 in response to laboratory strains of E. coli in vitro. We investigated the ability of UPEC to alter epithelial cytokine signaling by examining the in vitro responses of bladder epithelial cell lines to the cystitis strains UTI89 and NU14. The cystitis strains induced significantly less IL-6 than did the laboratory E. coli strain MG1655 from 5637 and T24 bladder epithelial cells. The cystitis strains also suppressed epithelial cytokine responses to exogenous lipopolysaccharide (LPS) and to laboratory E. coli. We found that insertional mutations in the rfa and rfb operons and in the surA gene all abolished the ability of UTI89 to suppress cytokine induction. The rfa and rfb operons encode LPS biosynthetic genes, while surA encodes a periplasmic cis-trans prolyl isomerase important in the biogenesis of outer membrane proteins. We conclude that, in this in vitro model system, cystitis strains of UPEC have genes encoding factors that suppress proinflammatory cytokine production by bladder epithelial cells.
Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8230, Saint Louis, Missouri 63110-1093, USA.
David A
DA
Hunstad
Sheryl S
SS
Justice
Chia S
CS
Hung
Scott R
SR
Lauer
Scott J
SJ
Hultgren
D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000276:immunology; D004926:Escherichia coli / Q000472:pathogenicity*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000096:biosynthesis / Q000494:pharmacology; D009876:Operon; D001743:Urinary Bladder / Q000276:immunology*
D015850:Interleukin-6; D008070:Lipopolysaccharides