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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
- Source :
- mSphere, Vol 4, Iss 6, p e00545-19 (2019), mSphere
- Publication Year :
- 2019
-
Abstract
- Interleukin-10 is part of the immune response to urinary tract infection (UTI) due to E. coli, and it is important in the early control of infection in the bladder. Defining the mechanism of engagement of the immune system by the bacteria that enables the protective IL-10 response is critical to exploring how we might exploit this mechanism for new infection control strategies. In this study, we reveal part of the bacterial flagellar apparatus (FliC) is an important component that is sensed by and responsible for induction of IL-10 in the response to UPEC. We show this response occurs in a TLR5-dependent manner. Using infection prevention and control trials in mice infected with E. coli, this study also provides evidence that purified FliC might be of value in novel approaches for the treatment of UTI or in preventing infection by exploiting the FliC-triggered bladder transcriptome.<br />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 therapeutic administration 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. IMPORTANCE Interleukin-10 is part of the immune response to urinary tract infection (UTI) due to E. coli, and it is important in the early control of infection in the bladder. Defining the mechanism of engagement of the immune system by the bacteria that enables the protective IL-10 response is critical to exploring how we might exploit this mechanism for new infection control strategies. In this study, we reveal part of the bacterial flagellar apparatus (FliC) is an important component that is sensed by and responsible for induction of IL-10 in the response to UPEC. We show this response occurs in a TLR5-dependent manner. Using infection prevention and control trials in mice infected with E. coli, this study also provides evidence that purified FliC might be of value in novel approaches for the treatment of UTI or in preventing infection by exploiting the FliC-triggered bladder transcriptome.
- Subjects :
- 0301 basic medicine
Time Factors
Urinary Bladder
030106 microbiology
lcsh:QR1-502
uropathogenic escherichia coli
Context (language use)
Inflammation
Biology
urologic and male genital diseases
medicine.disease_cause
Microbiology
lcsh:Microbiology
Host-Microbe Biology
Cell Line
Transcriptome
03 medical and health sciences
Immune system
medicine
Animals
Humans
Molecular Biology
Escherichia coli
Escherichia coli Infections
Innate immune system
Escherichia coli Proteins
Gene Expression Profiling
Epithelial Cells
Models, Theoretical
Immunity, Innate
female genital diseases and pregnancy complications
Interleukin-10
3. Good health
Mice, Inbred C57BL
Disease Models, Animal
Toll-Like Receptor 5
Interleukin 10
030104 developmental biology
TLR5
bacteria
flagella
medicine.symptom
urinary tract infection
Research Article
Flagellin
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- mSphere, Vol 4, Iss 6, p e00545-19 (2019), mSphere
- Accession number :
- edsair.doi.dedup.....6bc00f29d9a77be4a9ff43391d9851e1