The effects of cytotoxic necrotizing factor 1 expression in the uptake of<i>Escherichia coli</i>K1 by macrophages and the onset of meningitis in newborn mice

Chang, Alexander; Krishnan, Subramanian; Prasadarao, Nemani V.

doi:10.1080/21505594.2016.1192730

Cited by 11 publications

(17 citation statements)

References 39 publications

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“…Renal DC are resident cells important for innate immunity and bacterial clearance during pyelonephritis [ 36 , 40 ]. In addition, CNF1 has recently been shown to alter E. coli uptake by macrophages [ 41 ]. In response to renal injury, renal DC migrate to draining LNs where they present antigens [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

Cytotoxic Necrotizing Factor-1 (CNF1) does not promote E. coli infection in a murine model of ascending pyelonephritis

et al. 2017

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BackgroundUrinary tract infections (UTI) are among the most common and costly infections in both hospitalized and ambulatory patients. Uropathogenic E. coli (UPEC) represent the majority of UTI isolates and are a diverse group of bacteria that utilize a variety of virulence factors to establish infection of the genitourinary tract. The virulence factor cytotoxic necrotizing factor-1 (CNF1) is frequently expressed in clinical UPEC isolates. To date, there have been conflicting reports on the role of CNF1 in the pathogenesis of E. coli urinary tract infections.ResultsWe examined the importance of CNF1 in a murine ascending kidney infection/ pyelonephritis model by performing comparative studies between a clinical UPEC isolate strain and a CNF1-deletion mutant. We found no alterations in bacterial burden with the loss of CNF1, whereas loss of the virulence factor fimH decreased bacterial burdens. In addition, we found no evidence that CNF1 contributed to the recruitment of inflammatory infiltrates in the kidney or bladder in vivo.ConclusionsWhile further examination of CNF-1 may reveal a role in UTI pathogenesis, our data casts doubt on the role of CNF-1 in the pathogenesis of UPEC UTI. As with other infections, different models and approaches are needed to elucidate the contribution of CNF1 to E. coli UTI.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-017-1036-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Cytotoxic Necrotizing Factor-1 (CNF1) does not promote E. coli infection in a murine model of ascending pyelonephritis

et al. 2017

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“…Hemolysin of Proteus mirabilis and group B Streptococcus can also induce IL-1β secretion via NLRP3 inflammasome and enhance inflammation 16,17 . In UTI and meningitis animal models, E. coli CNF exacerbates inflammation 18,19 . CNF can synergistically promote IL-1β secretion with lipopolysaccharide in a caspase-1/caspase-11-dependent manner 20 .…”

Section: Introductionmentioning

confidence: 99%

Differential interleukin-1β induction by uropathogenic Escherichia coli correlates with its phylotype and serum C-reactive protein levels in Korean infants

Jung

Hong

Gharderpour

et al. 2019

Sci Rep

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Urinary tract infection (UTI) is one of the most common bacterial infections in infants less than age 1 year. UTIs frequently recur and result in long-term effects include sepsis and renal scarring. Uropathogenic Escherichia coli (UPEC), the most prevalent organism found in UTIs, can cause host inflammation via various virulence factors including hemolysin and cytotoxic necrotizing factors by inducing inflammatory cytokines such as interleukin (IL)-1β. However, the ability of each UPEC organism to induce IL-1β production may differ by strain. Furthermore, the correlation between differential IL-1β induction and its relevance in pathology has not been well studied. In this study, we isolated UPEC from children under age 24 months and infected bone-marrow derived macrophages with the isolates to investigate secretion of IL-1β. We found that children with higher concentrations of C-reactive protein (CRP) were more likely to harbor phylotype B2 UPEC strains that induced more IL-1β production than phylotype D. We also observed a significant correlation between serum CRP level and in vitro IL-1β induction by phylotype B2 UPEC bacteria. Our results highlight the diversity of UPEC in terms of IL-1β induction capacity in macrophages and suggest a potential pathogenic role in UTIs by inducing inflammation in infants.

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“…After bacterial secretion, CNF1 enters host cells by receptor-mediated endocytosis [ 3 ]. Two cellular receptors have so far been shown to mediate CNF1 internalization; the 37/67 kDa laminin receptor and the Lutheran adhesion glycoprotein/basal cell adhesion molecule (Lu/BCAM) [ 4 , 5 , 6 , 7 ]. Following endocytosis, endosomal acidification and cleavage of CNF1 leads to translocation of the active part of the toxin into the cytoplasm where it deamidates a specific glutamine residue in Rho GTPase proteins.…”

Section: Introductionmentioning

confidence: 99%

The Bacterial Toxin CNF1 Induces Activation and Maturation of Human Monocyte-Derived Dendritic Cells

Gall-Mas

Fabbri

Namini

et al. 2018

IJMS

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Cytotoxic necrotizing factor 1 (CNF1) is a bacterial protein toxin primarily expressed by pathogenic Escherichia coli strains, causing extraintestinal infections. The toxin is believed to enhance the invasiveness of E. coli by modulating the activity of Rho GTPases in host cells, but it has interestingly also been shown to promote inflammation, stimulate host immunity and function as a potent immunoadjuvant. The mechanisms underlying the immunostimulatory properties of CNF1 are, however, poorly characterized, and little is known about the direct effects of the toxin on immune cells. Here, we show that CNF1 induces expression of maturation markers on human immature monocyte-derived dendritic cells (moDCs) without compromising cell viability. Consistent with the phenotypic maturation, CNF1 further triggered secretion of proinflammatory cytokines and increased the capacity of moDCs to stimulate proliferation of allogenic naïve CD4+ T cells. A catalytically inactive form of the toxin did not induce moDC maturation, indicating that the enzymatic activity of CNF1 triggers immature moDCs to undergo phenotypic and functional maturation. As the maturation of dendritic cells plays a central role in initiating inflammation and activating the adaptive immune response, the present findings shed new light on the immunostimulatory properties of CNF1 and may explain why the toxin functions as an immunoadjuvant.

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The effects of cytotoxic necrotizing factor 1 expression in the uptake ofEscherichia coliK1 by macrophages and the onset of meningitis in newborn mice

Cited by 11 publications

References 39 publications

Cytotoxic Necrotizing Factor-1 (CNF1) does not promote E. coli infection in a murine model of ascending pyelonephritis

Cytotoxic Necrotizing Factor-1 (CNF1) does not promote E. coli infection in a murine model of ascending pyelonephritis

Differential interleukin-1β induction by uropathogenic Escherichia coli correlates with its phylotype and serum C-reactive protein levels in Korean infants

The Bacterial Toxin CNF1 Induces Activation and Maturation of Human Monocyte-Derived Dendritic Cells

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