Restriction of chronicEscherichia coliurinary tract infection depends upon T cell-derived interleukin-17, a deficiency of which predisposes to flagella-driven bacterial persistence

[摘要] Urinary tract infections (UTI) frequently progress to chronicity in infected individuals but the mechanisms of pathogenesis underlying chronic UTI are not well understood. We examined the role of interleukin (IL)-17A in UTI because this cytokine promotes innate defense against uropathogenicEscherichia coli(UPEC). Analysis of UPEC persistence and pyelonephritis in mice deficient in IL-17A revealed that UPEC CFT073 caused infection at a rate higher than the multidrug resistant strain EC958.Il17a(-/-)mice exhibited pyelonephritis with kidney bacterial burdens higher than those of wild-type (WT) mice. Synthesis of IL-17A in the bladder reflected a combination of gamma delta-T and T(H)17 cell responses. Analysis of circulating inflammatory mediators at 24h postinoculation identified predictors of progression to chronicity, including IL-6 and monocyte chemoattractant protein-1 (MCP-1). Histological analysis identified infiltrating populations of neutrophils, NK cells, and gamma delta T cells in the bladder, whereas neutrophils predominated in the kidney. Analysis of the contribution of flagella to chronicity using hyper-flagellated andfliC-deficient UPEC in WT andIl17a(-/-)mice revealed that, in a host that is deficient for the production of IL-17A, flagella contribute to bacterial persistence. These findings show a role for IL-17A in defense against chronic UTI and a contribution of flagella to the pathogenesis of infection.

[发布日期] 2020-11-01

[关键词] UROPATHOGENIC ESCHERICHIA-COLI;DENDRITIC CELLS;EXPRESSION;BLADDER;INNATE;INFLAMMATION;MICE;COLONIZATION;EPIDEMIOLOGY;ACTIVATION