Dataset Information

Eosinophils Control Liver Damage by Modulating Immune Responses Against Fasciola hepatica.

ABSTRACT: Eosinophils are granulocytes that participate in the defense against helminth parasites and in hypersensitivity reactions. More recently, eosinophils were shown to have other immunomodulatory functions, such as tissue reparation, metabolism regulation, and suppression of Th1 and Th17 immune responses. In the context of parasitic helminth infections, eosinophils have a controversial role, as they can be beneficial or detrimental for the host. In this work, we investigate the role of eosinophils in an experimental infection in mice with the trematode parasite Fasciola hepatica, which causes substantial economical losses around the world due to the infection of livestock. We demonstrate that eosinophils are recruited to the peritoneal cavity and liver from F. hepatica-infected mice and this recruitment is associated with increased levels of CCL11, TSLP, and IL-5. Moreover, the characterization of peritoneal and hepatic eosinophils from F. hepatica-infected mice showed that they express distinctive molecules of activation and cell migration. Depletion of eosinophils with an anti-Siglec-F antibody provoked more severe clinical signs and increased liver damage than control animals which were accompanied by an increase in the production of IL-10 by hepatic and splenic CD4+ T cells. In addition, we also report that eosinophils participate in the modulation of humoral immune responses during F. hepatica infection, contributing to their degranulation. In conclusion, we demonstrate that eosinophils are beneficial for the host during F. hepatica infection, by limiting the production of IL-10 by specific CD4+ T cells and favoring eosinophil degranulation induced by specific antibodies. This work contributes to a better understanding of the role of eosinophils in parasitic helminth infections.

SUBMITTER: Frigerio S

PROVIDER: S-EPMC7530260 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Eosinophils Control Liver Damage by Modulating Immune Responses Against <i>Fasciola hepatica</i>.

Frigerio Sofía S da Costa Valeria V Costa Monique M Festari María Florencia MF Landeira Mercedes M Rodríguez-Zraquia Santiago A SA Härtel Steffen S Toledo Jorge J Freire Teresa T

Frontiers in immunology 20200918

Eosinophils are granulocytes that participate in the defense against helminth parasites and in hypersensitivity reactions. More recently, eosinophils were shown to have other immunomodulatory functions, such as tissue reparation, metabolism regulation, and suppression of Th1 and Th17 immune responses. In the context of parasitic helminth infections, eosinophils have a controversial role, as they can be beneficial or detrimental for the host. In this work, we investigate the role of eosinophils i ...[more]

PMID: 33042162

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Project description:BACKGROUND:Snails such as Galba truncatula are hosts for trematode flukes causing fascioliasis, a zoonosis that is a major public health problem. Galba truncatula has recently been shown to be a cryptic species complex. African populations of Galba spp. are not yet studied using molecular assessments and is imperative to do so and reconstruct the centre of origin of Galba and to understand when and by what means it may have colonized the highlands of Africa and to what extent humans might have been involved in that process. METHODS:Samples from all known sub-ranges throughout Africa and new samples from Europe and Asia were obtained. We used a combination of two mitochondrial (cox1 and 16S) and one nuclear (ITS2) markers and phylogenetic, divergence time estimates and phylogeographical methods to determine the identity and biogeographical affinities. We also reconstructed the colonization history including the likely mode of dispersal and tested for the presence of cryptic Galba species in Africa. RESULTS:Galba truncatula is restricted to the Palaearctic region of the continent, namely Morocco. All sub-Saharan populations proved to be a distinct species according to the phylogenetic analyses and genetic distance. We propose to use the existing name Galba mweruensis (Connolly, 1929) for this species which is morphologically indistinguishable from the other two species hitherto known to occur in northern Africa, i.e. G. truncatula and G. schirazensis. Sub-tropical Africa has been colonized only once in either the Pliocene and possibly Miocene. Diversification within G. mweruensis is dated to the Plio-Pleistocene and thus human-mediated dispersal can be ruled out for the initial colonization of the isolated mountain ranges. There are potentially even more cryptic species in high altitude areas of Africa as outlined by the distinctness of the population found at the top of Mt. Elgon, Uganda. CONCLUSIONS:From a novel genetic inspection of available African material, a hitherto neglected distinct species, G. mweruensis, now appears a major host of F. hepatica throughout sub-Saharan Africa. A closer examination of trematode parasites hosted by this species is needed in order to understand transmission patterns in highlands throughout eastern and southern Africa. We encourage future studies to inspect other high altitudes areas in Africa in light of parasites of either veterinary or medical importance.

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

Eosinophils Control Liver Damage by Modulating Immune Responses Against Fasciola hepatica.

Publications

Eosinophils Control Liver Damage by Modulating Immune Responses Against <i>Fasciola hepatica</i>.

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