Rapid bladder interleukin-10 synthesis in response to uropathogenic Escherichia coli is part of a defense strategy triggered by the major bacterial flagellar filament fliC and contingent on TLR5

Acharya, Dhruba, Sullivan, Matthew J., Duell, Benjamin L., Goh, Kelvin G. K., Katupitiya, Lahiru, Gosling, Dean, Chamoun, Michelle N., Kakkanat, Asha, Chattopadhyay, Debasish, Crowley, Michael, Crossman, David K., Schembri, Mark A. and Uletta, Glen C. (2019) Rapid bladder interleukin-10 synthesis in response to uropathogenic Escherichia coli is part of a defense strategy triggered by the major bacterial flagellar filament fliC and contingent on TLR5. mSphere, 4 (6). ISSN 2379-5042

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Abstract

Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) engages interleukin-10 (IL-10) as an early innate immune response to regulate inflammation and promote the control of bladder infection. However, the mechanism of engagement of innate immunity by UPEC that leads to elicitation of IL-10 in the bladder is unknown. Here, we identify the major UPEC flagellar filament, FliC,as a key bacterial component sensed by the bladder innate immune system responsible for the induction of IL-10 synthesis. IL-10 responses of human as well as mouse bladder epithelial cell-monocyte cocultures were triggered by flagella of three major UPEC representative strains, CFT073, UTI89, and EC958. FliC purified to homogeneity induced IL-10 in vitro and in vivo as well as other functionally related cytokines, including IL-6. The genome-wide innate immunological context of FliC-induced IL-10 in the bladder was defined using RNA sequencing that revealed a network of transcriptional and antibacterial defenses comprising 1,400 genes that were induced by FliC. Of the FliC-responsive bladder transcriptome, altered expression of il10 and 808 additional genes were dependent on Toll-like receptor 5 (TLR5), according to analysis of TLR5-deficient mice. Examination of the potential of FliC and associated innate immune signature in the bladder to boost host defense, based on prophylactic or therapeuticadministration to mice, revealed significant benefits for the control of UPEC. We conclude that detection of FliC through TLR5 triggers rapid IL-10 synthesis in the bladder, and FliC represents a potential immune modulator that might offer benefit for the treatment or prevention of UPEC UTI.

Item Type: Article
Additional Information: Funding Information: This study was supported with funding from the National Medical Research Council (NHMRC; Australia) under grant number APP1084889 (G.C.U.).
Uncontrolled Keywords: flagella,urinary tract infection,uropathogenic escherichia coli,microbiology,molecular biology ,/dk/atira/pure/subjectarea/asjc/2400/2404
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Depositing User: LivePure Connector
Date Deposited: 15 Aug 2022 10:30
Last Modified: 18 Sep 2022 20:40
URI: https://ueaeprints.uea.ac.uk/id/eprint/87241
DOI: 10.1128/mSphere.00545-19

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