{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T09:27:36Z","timestamp":1792747656781,"version":"4.5.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:00:00Z","timestamp":1683763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2017YFD0501200"],"award-info":[{"award-number":["2017YFD0501200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2017YFD0501305"],"award-info":[{"award-number":["2017YFD0501305"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p><jats:italic>Clonorchis sinensis<\/jats:italic> is a zoonotic parasite associated with liver fibrosis and cholangiocarcinoma development. The role of toll-like receptors (TLRs) in <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infection has not yet been fully elucidated. Here, the TLR3 signaling pathway, cytokine expression and liver fibrosis were examined in <jats:italic>C<\/jats:italic>. <jats:italic>sinensis-<\/jats:italic>infected wildtype (WT) and <jats:italic>TLR3<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> mice. Polyinosinic-polycytidylic acid (Poly (I:C)) was used to treat <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> infections. The results showed that TLR3 deficiency caused severe clonorchiasis with increased parasite burden, exacerbated proinflammatory cytokine expression and liver lesions, promoted the TGF-\u03b21\/Smad2\/3 pathway and myofibroblast activation, exacerbated liver fibrosis (compared to WT mice). Poly (I:C) intervention increased the body weight, decreased mouse mortality and parasite burden, reduced liver inflammation, and alleviated <jats:italic>C<\/jats:italic>. <jats:italic>sinensis-<\/jats:italic>induced liver fibrosis. Furthermore, <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic> extracellular vesicles (CsEVs) promote the production of IL-6, TNF in WT biliary epithelial cells (BECs) via p38\/ERK pathway, compared with control group, while TLR3 deletion induced much higher levels of IL-6 and TNF in <jats:italic>TLR3<\/jats:italic><jats:sup>-\/-<\/jats:sup> BECs than that in WT BECs. Taken together, TLR3 inhibit IL-6 and TNF production via p38\/ERK signaling pathway, a phenomenon that resulted in the alleviation of <jats:italic>C<\/jats:italic>. <jats:italic>sinensis<\/jats:italic>-induced liver fibrosis. Poly (I:C) is a potential treatment for clonorchiasis.<\/jats:p>","DOI":"10.1371\/journal.pntd.0011325","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T17:22:00Z","timestamp":1683825720000},"page":"e0011325","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["TLR3 activation by Clonorchis sinensis infection alleviates the fluke-induced liver 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