Uropathogenic Escherichia coli dominantly suppress the innate immune response of bladder epithelial cells by a lipopolysaccharide- and Toll-like receptor 4-independent pathway

Hilbert, David W.; Pascal, Kristen E.; Libby, Erika; Mordechai, Eli; Adelson, Martin E.; Trama, Jason P.

doi:10.1016/j.micinf.2007.10.012

Cited by 38 publications

(41 citation statements)

References 42 publications

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“…We did not observe suppression of cytokine expression and/or neutrophil recruitment by our UPEC strains, regardless of HlyA1 production, by 6 h (data not shown) or 24 h after inoculation, as has previously been reported by others (46,(54)(55)(56)(57)(58). These groups measured the cytokine IL-6 and/or IL-8 after infection of different strains of bladder epithelial cell lines with clinical isolates (NU14, F11, UTI89) or with laboratory strains (HB101, MG1655) and showed that the laboratory strains induced significantly more cytokine release than the clinical isolates (54)(55)(56)(57).…”

Section: Resultssupporting

confidence: 89%

“…These groups measured the cytokine IL-6 and/or IL-8 after infection of different strains of bladder epithelial cell lines with clinical isolates (NU14, F11, UTI89) or with laboratory strains (HB101, MG1655) and showed that the laboratory strains induced significantly more cytokine release than the clinical isolates (54)(55)(56)(57). In addition, Loughman and Hunstad observed a reduction in neutrophil recruitment to the mouse bladder after challenge with UPEC strain UTI89 or CFT073 compared to that after challenge with the laboratory strain MG1655 (58).…”

Section: Resultsmentioning

confidence: 99%

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Cytotoxic Necrotizing Factor 1 and Hemolysin from Uropathogenic Escherichia coli Elicit Different Host Responses in the Murine Bladder

et al. 2013

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Cytotoxic necrotizing factor 1 (CNF1) and hemolysin (HlyA1) are toxins produced by uropathogenic Escherichia coli (UPEC). We previously showed that these toxins contribute to the inflammation and tissue damage seen in a mouse model of ascending urinary tract infection. CNF1 constitutively activates small Rho GTPases by deamidation of a conserved glutamine residue, and HlyA1 forms pores in eukaryotic cell membranes. In this study, we used cDNA microarrays of bladder tissue isolated from mice infected intraurethrally with wild-type CP9, CP9cnf1, or CP9⌬hlyA to further evaluate the role that each toxin plays in the host response to UPEC. Regardless of the strain used, we found that UPEC itself elicited a significant change in host gene expression 24 h after inoculation. The largest numbers of upregulated genes were in the cytokine and chemokine signaling and Toll-like receptor signaling pathways. CNF1 exerted a strong positive influence on expression of genes involved in innate immunity and signal transduction and a negative impact on metabolism-and transport-associated genes. HlyA1 evoked an increase in expression of genes that encode innate immunity factors and a decrease in expression of genes involved in cytoskeletal and metabolic processes. Multiplex cytokine and myeloperoxidase assays corroborated our finding that a strong proinflammatory response was elicited by all strains tested. Bladders challenged intraurethrally with purified CNF1 displayed pathology similar to but significantly less intense than the pathology that we observed in CP9-challenged mice. Our data demonstrate substantial roles for CNF1 and HlyA1 in initiation of a strong proinflammatory response to UPEC in the bladder. U rinary tract infections (UTIs) are the most common bacterial infection in women and affect over 50% of women at some time throughout their lifetime (1). The clinical manifestations of UTIs vary from mild to severe, and common symptoms include dysuria, hematuria, pyuria, urinary frequency and urgency, suprapubic pain, and fever. The annual cost in the United States for diagnosis and treatment of UTIs is over $3 billion (2). Uncomplicated UTIs occur when commensal bacteria from the gastrointestinal (GI) tract transit to the periurethral area or vaginal introitus. The bacteria are then introduced into the urethra and ascend into the bladder to cause cystitis and, in more severe cases, into the kidneys to cause pyelonephritis (3-5). The etiological agents of 85% of uncomplicated UTIs are uropathogenic Escherichia coli (UPEC), a subgroup of extraintestinal pathogenic E. coli (1). UPEC expresses virulence factors that specifically facilitate colonization of and replication within the urinary tract.Cytotoxic necrotizing factor 1 (CNF1) is an ϳ115-kDa toxin that is expressed by ϳ40% of UPEC isolates and up to 30% of diarrheal E. coli isolates (6). CNF1 constitutively activates small Rho-family GTPases via deamidation of glutamine 63 of RhoA and glutamine 61 in Rac1 and Cdc42 (7,8). Constitutive activation of these small GTPases by C...

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Cytotoxic Necrotizing Factor 1 and Hemolysin from Uropathogenic Escherichia coli Elicit Different Host Responses in the Murine Bladder

et al. 2013

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“…The interaction between UPEC and the bladder epithelial cells is important during establishment of a UTI [7,13]. Epithelial cells are the first line of host defense against invading pathogens [9].…”

Section: Discussionmentioning

confidence: 99%

“…Of the numerous bacteria that can cause UTIs, Escherichia coli is the most frequent infectious agent and is responsible for >80% of all UTIs [7,31]. Commensal E. coli in the intestinal tract colonizes the vaginal and periuretheral tissues, ascend into the bladder, and cause a UTI [7,32].…”

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confidence: 99%

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Characterization and Zoonotic Potential of Uropathogenic Escherichia coli Isolated from Dogs

Nam

Ko²,

Chae³

et al. 2013

J. Microbiol. Biotechnol.

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The aim of this study was to investigate the characteristics of canine uropathogenic Escherichia coli (UPEC) and the interaction between canine UPEC and human bladder epithelial cells. Ten E. coli isolates collected from dogs with cystitis were analyzed for antimicrobial resistance patterns, the presence of virulence factors, and biofilm formation. The ability of these isolates to induce cytotoxicity, invade human bladder epithelial cells, and stimulate an immune response was also determined. We observed a high rate of antimicrobial resistance among canine UPEC isolates. All virulence genes tested (including adhesins, iron acquisition, and protectin), except toxin genes, were detected among the canine UPEC isolates. We found that all isolates showed varying degrees of biofilm formation (mean, 0.26; range, 0.07 to 0.82), using a microtiter plate assay to evaluate biofilm formation by the isolates. Cytotoxicity to human bladder epithelial cells by the canine UPEC isolates increased in a time-dependent manner, with a 56.9% and 36.1% reduction in cell viability compared with the control at 6 and 9 h of incubation, respectively. We found that most canine UPEC isolates were able to invade human bladder epithelial cells. The interaction between these isolates and human bladder epithelial cells strongly induced the production of proinflammatory cytokines such as IL-6 and IL-8. We demonstrated that canine UPEC isolates can interact with human bladder epithelial cells, although the detailed mechanisms remain unknown. The results suggest that canine UPEC isolates, rather than dogspecific pathogens, have zoonotic potential.

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A Murine Model for Escherichia coli Urinary Tract Infection

Hannan

Hunstad

2016

Methods in Molecular Biology

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Urinary tract infections (UTI) are among the most common bacterial infections of humans. The mouse provides an excellent and tractable model system for cystitis and pyelonephritis caused by Escherichia coli and other uropathogens. Using a well-established model of experimental cystitis in which the bladders of female mice are infected via transurethral catheterization, the molecular details of the pathogenesis of bacterial cystitis have been substantially illuminated in the last decade. Uropathogenic E. coli attach to bladder epithelium (both in human and mouse) via adhesive type 1 pili, establish a replicative niche within epithelial cell cytoplasm, and form intracellular bacterial communities that are protected from antibiotic effects and immune clearance. The use of different inbred and mutant mouse strains offers the opportunity to study outcomes of infection, including resolution, formation of quiescent intracellular bacterial reservoirs, chronic bacterial cystitis, and recurrent infections. Urine, bladder, and kidney tissues can be analyzed by bacterial culture, histology, immunohistochemistry, immunofluorescent and confocal microscopy, electron microscopy, and flow cytometry, while a broad array of soluble markers (e.g., cytokines) can also be profiled in serum, urine, and tissue homogenates by ELISA, Western blotting, multiplex bead array, and other approaches. This model promises to afford continued opportunity for discovery of pathogenic mechanisms and evaluation of therapeutic and preventive strategies for acute, chronic, and recurrent UTI.

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Uropathogenic Escherichia coli dominantly suppress the innate immune response of bladder epithelial cells by a lipopolysaccharide- and Toll-like receptor 4-independent pathway

Cited by 38 publications

References 42 publications

Cytotoxic Necrotizing Factor 1 and Hemolysin from Uropathogenic Escherichia coli Elicit Different Host Responses in the Murine Bladder

Cytotoxic Necrotizing Factor 1 and Hemolysin from Uropathogenic Escherichia coli Elicit Different Host Responses in the Murine Bladder

Characterization and Zoonotic Potential of Uropathogenic Escherichia coli Isolated from Dogs

A Murine Model for Escherichia coli Urinary Tract Infection

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