title: Attenuation of human neutrophil migration and function by uropathogenic bacteria.
abstract: The establishment of bacterial infections at mucosal epithelial surfaces is determined by the balance of virulence attributes of the pathogen with the activity of innate host defenses. Polymorphonuclear leukocytes (PMN) are key responders in many bacterial infections, but the mechanisms by which pathogens subvert these early responses to establish infection are largely undefined. Here, we model early interactions between human PMN and the primary cause of urinary tract infections, namely uropathogenic Escherichia coli (UPEC). Our objective was to define virulence phenotypes of uropathogens that permit evasion of PMN activity. We show that UPEC strains, as compared with laboratory and commensal E. coli, resist phagocytic killing and dampen the production of antimicrobial reactive oxygen species by PMN. Analysis of the transcriptional responses of PMN to E. coli strains revealed that UPEC exposure downregulates the expression of PMN genes that direct pro-inflammatory signaling and PMN chemotaxis, adhesion, and migration. Consistent with these data, UPEC attenuated transepithelial neutrophil recruitment in an in vitro model of acute infection and in a murine model of bacterial cystitis. We propose that these UPEC strategies are important in the establishment of epithelial infection, and that the findings are germane to bacterial infections at other epithelial surfaces.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO 63110-1093, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Loughman
authors.forename: David A
authors.initials: DA
authors.lastname: Hunstad
mesh_terms: D000328:Adult; D000818:Animals; D054441:Cell Migration Assays, Leukocyte; D002465:Cell Movement; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D057131:Immune Evasion; D051379:Mice; D050296:Microbial Viability; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D056689:Uropathogenic Escherichia coli / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D017382:Reactive Oxygen Species