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Fasciola hepatica soluble antigens (FhAg) induce ovine PMN innate immune reactions and NET formation in vitro and in vivo

datacite.subject.fosCiências Agrárias::Ciências Veterinárias
datacite.subject.sdg15:Proteger a Vida Terrestre
dc.contributor.authorMuñoz-Caro, Tamara
dc.contributor.authorGómez-Ceruti, Marcela
dc.contributor.authorSilva, Liliana M. R.
dc.contributor.authorGutiérrez-Expósito, Daniel
dc.contributor.authorWagner, Henrik
dc.contributor.authorTaubert, Anja
dc.contributor.authorHermosilla, Carlos
dc.date.accessioned2026-02-23T12:51:00Z
dc.date.available2026-02-23T12:51:00Z
dc.date.issued2023-11
dc.description.abstractFasciola hepatica causes liver fluke disease, a worldwide neglected and re-emerging zoonotic disease, leading to hepatitis in humans and livestock. In the pathogenesis, flukes actively migrate through liver parenchyma provoking tissue damage. Here, parasites must confront leukocytes of the innate immune system in vivo. Polymorphonuclear neutrophils (PMN) are the most abundant granulocytes and first ones arriving at infection sites. PMN may display neutrophil extracellular traps (NETs), consisting of nuclear DNA, decorated with histones, enzymes, and antimicrobial peptides. We investigated for the first time whether F. hepatica soluble antigens (FhAg) can also trigger NETosis and innate immune reactions in exposed ovine PMN. Thus, isolated PMN were co-cultured with FhAg and NET formation was visualized by immunofluorescence and scanning electron microscopy analyses resulting in various phenotypes with spread NETs being the most detected in vitro. In line, NETs quantification via Picogreen®-fluorometric measurements revealed induction of anchored- and cell free NETs phenotypes. Live cell 3D-holotomographic microscopy revealed degranulation of stimulated PMN at 30 min exposure to FhAg. Functional PMN chemotaxis assays showed a significant increase of PMN migration (p = 0.010) and intracellular ROS production significantly increased throughout time (p = 0.028). Contrary, metabolic activities profiles of FhAg-exposed PMN did not significantly increase. Finally, in vivo histopathological analysis on F. hepatica-parasitized liver tissue sections of sheep showed multifocal infiltration of inflammatory cells within liver parenchyma, and further fluorescence microscopy analyses confirmed NETs formation in vivo. Overall, we hypothesized that NET-formation is a relevant host defence mechanism that might have a role in the pathogenesis of fasciolosis in vivo.eng
dc.identifier.citationMuñoz-Caro, T., Gómez-Ceruti, M., Silva, L.M.R. et al. Fasciola hepatica soluble antigens (FhAg) induce ovine PMN innate immune reactions and NET formation in vitro and in vivo. Vet Res 54, 105 (2023). https://doi.org/10.1186/s13567-023-01236-z
dc.identifier.doi10.1186/s13567-023-01236-z
dc.identifier.issn1297-9716
dc.identifier.urihttp://hdl.handle.net/10400.26/61817
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSpringer Nature
dc.relation.hasversionhttps://doi.org/10.1186/s13567-023-01236-z
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectFasciola hepatica
dc.subjectneutrophil extracellular traps
dc.subjectNETosis
dc.subjectROS
dc.subjectinnate immunity
dc.subjectsheep
dc.subjectlivestock
dc.titleFasciola hepatica soluble antigens (FhAg) induce ovine PMN innate immune reactions and NET formation in vitro and in vivoeng
dc.typecontribution to journal
dspace.entity.typePublication
oaire.citation.startPage105
oaire.citation.titleVeterinary Research
oaire.citation.volume54
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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