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dc.contributor.authorChaiyadet, Sujittra
dc.contributor.authorSotillo-Gallego, Javier 
dc.contributor.authorKrueajampa, Watchara
dc.contributor.authorThongsen, Sophita
dc.contributor.authorSmout, Michael
dc.contributor.authorBrindley, Paul J.
dc.contributor.authorLaha, Thewarach
dc.contributor.authorLoukas, Alex
dc.identifier.citationFront Cell Infect Microbiol. 2022 Feb 11;12:827521.es_ES
dc.description.abstractInter-phylum transfer of molecular information is exquisitely exemplified in the uptake of parasite extracellular vesicles (EVs) by their target mammalian host tissues. The oriental liver fluke, Opisthorchis viverrini is the major cause of bile duct cancer in people in Southeast Asia. A major mechanism by which O. viverrini promotes cancer is through the secretion of excretory/secretory products which contain extracellular vesicles (OvEVs). OvEVs contain microRNAs that are predicted to impact various mammalian cell proliferation pathways, and are internalized by cholangiocytes that line the bile ducts. Upon uptake, OvEVs drive relentless proliferation of cholangiocytes and promote a tumorigenic environment, but the underlying mechanisms of this process are unknown. Moreover, purification and characterization methods for helminth EVs in general are ill defined. We therefore compared different purification methods for OvEVs and characterized the sub-vesicular compartment proteomes. Two CD63-like tetraspanins (Ov-TSP-2 and TSP-3) are abundant on the surface of OvEVs, and could serve as biomarkers for these parasite vesicles. Anti-TSP-2 and -TSP-3 IgG, as well as different endocytosis pathway inhibitors significantly reduced OvEV uptake and subsequent proliferation of cholangiocytes in vitro. Silencing of Ov-tsp-2 and tsp-3 gene expression in adult flukes using RNA interference resulted in substantial reductions in OvEV secretion, and those vesicles that were secreted were deficient in their respective TSP proteins. Our findings shed light on the importance of tetraspanins in fluke EV biogenesis and/or stability, and provide a conceivable mechanism for the efficacy of anti-tetraspanin subunit vaccines against a range of parasitic helminth infections.es_ES
dc.description.sponsorshipThis study was supported by the National Cancer Institute, National Institutes of Health, award no. 2R01CA164719-06A1 (TL, AL and PB) and Research and Graduate Studies, Khon Kaen University (TL and SC). AL is supported by a senior principal research fellowship (1117504) and program grant (1132975) from the National Health and Medical Research Council, Australia. The Transmission Microscopy facility at Khon Kaen University was supported by the Department of Anatomy, Faculty of Medicine, Khon Kaen University.es_ES
dc.publisherFrontiers Media es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subjectOpisthorchis viverrinies_ES
dc.subjectExtracellular vesiclees_ES
dc.subjectLiver flukees_ES
dc.titleSilencing of Opisthorchis viverrini Tetraspanin Gene Expression Results in Reduced Secretion of Extracellular Vesicleses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderKhon Kaen University (Tailandia)es_ES
dc.contributor.funderNIH - National Cancer Institute (NCI) (Estados Unidos)es_ES
dc.contributor.funderNational Health and Medical Research Council (Australia)es_ES
dc.identifier.journalFrontiers in Cellular and Infection Microbiologyes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES

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