PMID- 32901999 OWN - NLM STAT- MEDLINE DCOM- 20210430 LR - 20210430 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 34 IP - 11 DP - 2020 Nov TI - Restriction of chronic Escherichia coli urinary tract infection depends upon T cell-derived interleukin-17, a deficiency of which predisposes to flagella-driven bacterial persistence. PG - 14572-14587 LID - 10.1096/fj.202000760R [doi] AB - 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 uropathogenic Escherichia 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 gammadelta-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 gammadelta T cells in the bladder, whereas neutrophils predominated in the kidney. Analysis of the contribution of flagella to chronicity using hyper-flagellated and fliC-deficient UPEC in WT and Il17a(-/-) 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. CI - (c) 2020 Federation of American Societies for Experimental Biology. FAU - Chamoun, Michelle N AU - Chamoun MN AD - School of Medical Sciences, And Menzies Health Institute Queensland, Griffith University, Parklands, QLD, Australia. FAU - Sullivan, Matthew J AU - Sullivan MJ AD - School of Medical Sciences, And Menzies Health Institute Queensland, Griffith University, Parklands, QLD, Australia. FAU - Goh, Kelvin G K AU - Goh KGK AD - School of Medical Sciences, And Menzies Health Institute Queensland, Griffith University, Parklands, QLD, Australia. FAU - Acharya, Dhruba AU - Acharya D AD - School of Medical Sciences, And Menzies Health Institute Queensland, Griffith University, Parklands, QLD, Australia. FAU - Ipe, Deepak S AU - Ipe DS AD - School of Medical Sciences, And Menzies Health Institute Queensland, Griffith University, Parklands, QLD, Australia. FAU - Katupitiya, Lahiru AU - Katupitiya L AD - School of Medical Sciences, And Menzies Health Institute Queensland, Griffith University, Parklands, QLD, Australia. FAU - Gosling, Dean AU - Gosling D AD - School of Medical Sciences, And Menzies Health Institute Queensland, Griffith University, Parklands, QLD, Australia. FAU - Peters, Kate M AU - Peters KM AD - School of Chemistry and Molecular Biosciences, Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, Australia. FAU - Sweet, Matthew J AU - Sweet MJ AD - Institute for Molecular Bioscience (IMB), IMB Centre for Inflammation and Disease Research, Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD, Australia. FAU - Sester, David P AU - Sester DP AD - TRI Flow Cytometry Suite (TRI.fcs), Translational Research Institute, Wooloongabba, QLD, Australia. FAU - Schembri, Mark A AU - Schembri MA AD - School of Chemistry and Molecular Biosciences, Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD, Australia. FAU - Ulett, Glen C AU - Ulett GC AD - School of Medical Sciences, And Menzies Health Institute Queensland, Griffith University, Parklands, QLD, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200909 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Escherichia coli Proteins) RN - 0 (FliC protein, E coli) RN - 0 (Il17a protein, mouse) RN - 0 (Interleukin-17) RN - 12777-81-0 (Flagellin) SB - IM MH - Animals MH - Chemokine CCL2/metabolism MH - Escherichia coli Proteins/genetics/metabolism MH - Female MH - Flagella/genetics/*metabolism MH - Flagellin/genetics/metabolism MH - Host-Pathogen Interactions MH - *Immunity, Innate MH - Interleukin-17/genetics/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - T-Lymphocyte Subsets/*immunology MH - Urinary Bladder/cytology/immunology/microbiology MH - Urinary Tract Infections/genetics/*immunology/microbiology MH - Uropathogenic Escherichia coli/genetics/*pathogenicity/physiology OTO - NOTNLM OT - Escherichia coli OT - Gram-negative pathogens OT - bacterial pathogenesis OT - innate immunity OT - urinary tract infection EDAT- 2020/09/10 06:00 MHDA- 2021/05/01 06:00 CRDT- 2020/09/09 08:49 PHST- 2020/03/31 00:00 [received] PHST- 2020/07/30 00:00 [revised] PHST- 2020/08/18 00:00 [accepted] PHST- 2020/09/10 06:00 [pubmed] PHST- 2021/05/01 06:00 [medline] PHST- 2020/09/09 08:49 [entrez] AID - 10.1096/fj.202000760R [doi] PST - ppublish SO - FASEB J. 2020 Nov;34(11):14572-14587. doi: 10.1096/fj.202000760R. Epub 2020 Sep 9.