Dataset Information

Fasciola hepatica GST downregulates NF-?B pathway effectors and inflammatory cytokines while promoting survival in a mouse septic shock model.

ABSTRACT: Parasitic helminths and helminth-derived molecules have demonstrated to possess powerful anti-inflammatory properties and confirmed therapeutic effects on inflammatory diseases. The helminth Fasciola hepatica has been reported to suppress specific Th1 specific immune responses induced by concurrent bacterial infections, thus demonstrating its anti-inflammatory ability in vivo. In this study, we demonstrate that native F. hepatica glutathione S-transferase (nFhGST), a major parasite excretory-secretory antigen, majorly comprised of Mu-class GST isoforms, significantly suppresses the LPS-induced TNF? and IL1? of mouse bone-marrow derived macrophages in vitro and the pro-inflammatory cytokine/chemokine storm within C57BL/6 mice exposed to lethal doses of LPS increasing their survival rate by more than 85%. Using THP1-Blue CD14 cells, a human monocyte cell line, we also demonstrate that nFhGST suppresses NF-?B activation in response to multiple TLR-ligands, including whole bacteria clinical isolates and this suppression was found to be dose-dependent and independent of the timing of exposure. Moreover, the suppressive effect of nFhGST on NF-?B activation was shown to be independent of enzyme activity or secondary structure of protein. As part of its anti-inflammatory effect nFhGST target multiple proteins of the canonic and non-canonic NF-?B signaling pathway as well as also JAK/STAT pathway. Overall, our results demonstrate the potent anti-inflammatory properties of nFhGST and its therapeutic potential as an anti-inflammatory agent.

SUBMITTER: Aguayo V

PROVIDER: S-EPMC6381083 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Fasciola hepatica GST downregulates NF-κB pathway effectors and inflammatory cytokines while promoting survival in a mouse septic shock model.

Aguayo Vasti V Valdés Fernandez Bianca N BN Rodríguez-Valentín Madeline M Ruiz-Jiménez Caleb C Ramos-Benítez Marcos J MJ Méndez Loyda B LB Espino Ana M AM

Scientific reports 20190219 1

Parasitic helminths and helminth-derived molecules have demonstrated to possess powerful anti-inflammatory properties and confirmed therapeutic effects on inflammatory diseases. The helminth Fasciola hepatica has been reported to suppress specific Th1 specific immune responses induced by concurrent bacterial infections, thus demonstrating its anti-inflammatory ability in vivo. In this study, we demonstrate that native F. hepatica glutathione S-transferase (nFhGST), a major parasite excretory-sec ...[more]

PMID: 30783117

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Project description:BackgroundFasciola hepatica (liver fluke) affects grazing animals including horses but the extent to which it affects UK horses is unknown.ObjectivesTo define how liver fluke affects the UK horse population.Study designDescriptive, cross-sectional, observational study.MethodsAn F. hepatica excretory-secretory antibody detection ELISA with a diagnostic sensitivity of 71% and specificity of 97% was validated and used to analyse serum samples. An abattoir study was performed to determine prevalence. A case-control study of 269 horses compared fluke exposure between horses with liver disease and controls. Data on clinical signs and blood test results were collected for sero-positive horses. Genotyping of adult fluke was used to produce a multilocus genotype for each parasite.ResultsFour (2.2%) of 183 horses registered in the UK, sampled in the abattoir, had adult flukes in the liver, and the sero-prevalence of F. hepatica was estimated as 8.7%. In the case-control study, horses showing signs consistent with liver disease had significantly higher odds of testing positive for F. hepatica on ELISA than control horses. In 23 sero-positive horses, a range of non-specific clinical signs and blood test abnormalities was reported, with a third of the horses showing no signs. Genotypic analysis of liver flukes from horses provided evidence that these came from the same population as flukes from sheep and cattle.Main limitationsBias could have arisen in the prevalence and case-control studies due to convenience sampling methods, in particular the geographic origin of the horses. Only a small number of horses tested positive so the data on clinical signs are limited.ConclusionsExposure to liver fluke occurs frequently in horses and may be an under-recognised cause of liver disease. Flukes isolated from horses are from the same population as those found in ruminants. When designing and implementing parasite control plans, fluke should be considered, and horses should be tested if appropriate.

Dataset Information

Fasciola hepatica GST downregulates NF-?B pathway effectors and inflammatory cytokines while promoting survival in a mouse septic shock model.

Publications

Fasciola hepatica GST downregulates NF-κB pathway effectors and inflammatory cytokines while promoting survival in a mouse septic shock model.

Similar Datasets

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