Effect of Vaginal Fluid on Adherence of Type 1 Piliated Escherichia coli to Epithelial Cells

Gaffney, Robert A.; Venegas, Mario F.; Kanerva, Claire; Navas, Elena L.; Anderson, Byron; Schaeffer, Anthony J.

doi:10.1093/infdis/172.6.1528

Cited by 25 publications

(17 citation statements)

References 24 publications

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“…Fecal and clinical strains were selected from the ECOR panel to represent a diversity of known virulence factor genes (21,30). Type 1 pilus expression was confirmed by a mannose-sensitive hemagglutination assay using guinea pig erythrocytes (Cleveland Scientific, OH) (10,19).…”

Section: Methodsmentioning

confidence: 99%

Modulation of Host Innate Immune Response in the Bladder by UropathogenicEscherichia coli

Billips¹,

Forrestal²,

Rycyk³

et al. 2007

Infect Immun

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Uropathogenic Escherichia coli (UPEC), the most frequent cause of urinary tract infection (UTI), is associated with an inflammatory response which includes the induction of cytokine/chemokine secretion by urothelial cells and neutrophil recruitment to the bladder. Recent studies indicate, however, that UPEC can evade the early activation of urothelial innate immune response in vitro. In this study, we report that infection with the prototypic UPEC strain NU14 suppresses tumor necrosis factor alpha (TNF-␣)-mediated interleukin-8 (CXCL-8) and interleukin-6 (CXCL-6) secretion from urothelial cell cultures compared to infection with a type 1 piliated E. coli K-12 strain. Furthermore, examination of a panel of clinical E. coli isolates revealed that 15 of 17 strains also possessed the ability to suppress cytokine secretion. In a murine model of UTI, NU14 infection resulted in diminished levels of mRNAs encoding keratinocyte-derived chemokine, macrophage inflammatory peptide 2, and CXCL-6 in the bladder relative to infection with an E. coli K-12 strain. Furthermore, reduced stimulation of inflammatory chemokine production during NU14 infection correlated with decreased levels of bladder and urine myeloperoxidase and increased bacterial colonization. These data indicate that a broad phylogenetic range of clinical E. coli isolates, including UPEC, may evade the activation of innate immune response in the urinary tract, thereby providing a pathogenic advantage.Urinary tract infections (UTI) are most frequently caused by an ascending colonization of the bladder and/or kidneys by Escherichia coli (9, 33). Infection of the urinary tract results in an inflammatory response characterized by increased levels of urinary cytokines and neutrophil influx (1, 13-15). The innate immune response to infection by uropathogenic E. coli (UPEC) depends upon activation of host pattern recognition receptors of the Toll-like receptor pathway, including Toll-like receptor 4 (TLR4) (5,16,(37)(38)(39). Recognition of E. coli lipopolysaccharide (LPS) by urothelial cells that express TLR4 results in activation of the proinflammatory and prosurvival NF-B pathway and secretion of chemokines/cytokines, including CXCL-6 and CXCL-8 (2). The resulting accumulation of inflammatory chemokines in the bladder mucosa and urine during UTI induces the recruitment of neutrophils, which leads to the clearance of bacteria and resolution of infection. Infection of the urinary tract by UPEC also induces adaptive immune responses characterized by humoral and cell-mediated responses which protect against future infection (42).Many pathogenic bacterial species possess the ability to modulate the innate immune response to evade host defenses and promote colonization, including several that block the activation of the NF-B pathway (7,31,32,35,36). We previously reported that UPEC strain NU14 blocks activation of the NF-B pathway and thereby promotes apoptosis (26,27). Insertional mutation of the genes encoding the periplasmic chaperone SurA or the LPS biosynthetic oper...

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Section: Methodsmentioning

confidence: 99%

Modulation of Host Innate Immune Response in the Bladder by UropathogenicEscherichia coli

Billips¹,

Forrestal²,

Rycyk³

et al. 2007

Infect Immun

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“…All bacterial strains were propagated in Luria broth at 37°C under static conditions to promote expression of type 1 pili (3). The extent of type 1 pilus expression was determined by mannose-sensitive hemagglutination (6,8) of guinea pig erythrocytes (Cleveland Scientific).…”

Section: Methodsmentioning

confidence: 99%

“…NU14 prevented the LPS-induced degradation of IB. (B) TEU-2 cells starved of growth factors were preincubated with the UPEC isolate NU14 or the piliated nonpathogen HB101/pWRS1-17 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). The cells were then stimulated with epidermal growth factor (EGF) (100 ng/ml) for 10 min, whole-cell lysates were prepared, and immunoblot analysis was performed using anti-phospho-Erk1/2 serum.…”

Section: Fig 4 Upec Inhibits Urothelial Nf-b Response To Tnf-␣mentioning

confidence: 99%

Uropathogenic Escherichia coli Potentiates Type 1 Pilus-Induced Apoptosis by Suppressing NF-κB

et al. 2001

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Urinary tract infections (UTIs) are among the most common inflammatory diseases. Acute UTIs are typically caused by type 1-piliated Escherichia coli and result in urothelial apoptosis, local cytokine release, and neutrophil infiltration. To examine the urothelial apoptotic response, a human urothelial cell line was incubated with various E. coli isolates and was then characterized by flow cytometry. Uropathogenic E. coli (UPEC) induced rapid urothelial apoptosis that was strictly dependent upon interactions mediated by type 1 pili. Interestingly, nonpathogenic HB101 E. coli expressing type 1 pili induced apoptosis at approximately 50% of the level induced by UPEC, suggesting that pathogenic strains contribute to apoptosis by pilus-independent mechanisms. Consistent with this possibility, UPEC blocked activity of an NF-B-dependent reporter in response to inflammatory stimuli, yet this effect was independent of functional type 1 pili and was not mediated by laboratory strains of E. coli. UPEC suppressed NF-B by stabilizing IB␣, and UPEC rapidly altered cellular signaling pathways. Finally, blocking NF-B activity increased the level of piliated HB101-induced apoptosis to the level of apoptosis induced by UPEC. These results suggest that UPEC blocks NF-B and thereby enhances type 1 pili-induced apoptosis as a component of the uropathogenic program.Urinary tract infections (UTIs) are among the most common infectious diseases, resulting in over 7 million clinic visits annually in the United States alone (7) and causing significant morbidity and mortality. The majority of UTIs are due to ascending infections of the urinary bladder (cystitis) by Escherichia coli that expresses type 1 pili, fibrous organelles that mediate attachment to mannosylated host cell proteins (reviewed in reference 19). The infection process results in bladder inflammation that causes symptoms such as pain and frequent or urgent voiding. Given the emergence of antibiotic-resistant strains of uropathogenic E. coli (UPEC) (A. J. Schaeffer, Editorial, Curr. Opin. Urol. 10:23-24, 2000), a more thorough understanding of pathogenic mechanisms is necessary to identify novel therapeutic targets for the treatment and prevention of UTIs.A key feature of inflammation during UTIs is a disruption of the urothelial integrity due to the exfoliation and subsequent excretion of superficial urothelial cells (4). Studies with mice have shown that UPEC induces a rapid loss of superficial urothelial cells, and the sloughing of superficial cells is due to the induction of apoptosis (12). This apoptotic process is dependent upon the expression of intact type 1 pili, since fimH mutant UPEC strains lacking the adhesin subunit FimH that forms the pilus tip fail to induce apoptosis, yet laboratory strains of E. coli induce apoptosis if they express intact type 1 pili. As a result of the urothelial apoptotic response, clearance of a majority of UPEC from the bladder occurs during voiding of urine. Thus, urothelial apoptosis is considered to be an important host defense in r...

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“…Bacteria were propagated in Luria broth at 37°C under static conditions that promote expression of type 1 pili (18). The extent of type 1 pilus expression was determined by mannose-sensitive hemagglutination (19,20) of guinea pig erythrocytes (Cleveland Scientific).…”

Section: Bacterial Strainsmentioning

confidence: 99%

Antigen-Specific Responses Accelerate Bacterial Clearance in the Bladder

Thumbikat¹,

Waltenbaugh

Schaeffer³

et al. 2006

The Journal of Immunology

100

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Urinary tract infections (UTIs) cause patient morbidity and have a substantial economic impact. Half of all women will suffer a UTI at least once, and 25% of these women will have recurrent infections. That 75% of previously infected women do not become reinfected strongly suggests a role for an adaptive immune response. The goal of this study was to characterize the adaptive immune responses to uropathogenic Escherichia coli (UPEC), the predominant uropathogen. A novel murine model of UTI reinfection was developed using the prototypic cystitis UPEC isolate NU14 harboring a plasmid encoding OVA as a unique antigenic marker. Bacterial colonization of the bladder was quantified following one or more infections with NU14-OVA. Animals developed anti-OVA serum IgG and IgM titers after the initial infection and marked up-regulation of activation markers on splenic T cells. We observed a 95% reduction in bacterial colonization upon reinfection, and splenic leukocytes showed Ag-specific proliferation in vitro. Adoptive transfer of splenic T cells or passive transfer of serum from previously infected mice protected naive syngeneic mice from UPEC colonization. These findings support our hypothesis that adaptive immune responses to UPEC protect the bladder from reinfection and form the basis of understanding susceptibility to recurrent UTI in women.

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Effect of Vaginal Fluid on Adherence of Type 1 Piliated Escherichia coli to Epithelial Cells

Cited by 25 publications

References 24 publications

Modulation of Host Innate Immune Response in the Bladder by UropathogenicEscherichia coli

Modulation of Host Innate Immune Response in the Bladder by UropathogenicEscherichia coli

Uropathogenic Escherichia coli Potentiates Type 1 Pilus-Induced Apoptosis by Suppressing NF-κB

Antigen-Specific Responses Accelerate Bacterial Clearance in the Bladder

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