{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T08:35:22Z","timestamp":1781858122740,"version":"3.54.5"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>During <jats:italic>Clonorchis sinensis<\/jats:italic> (<jats:italic>C. sinensis<\/jats:italic>) infection, pro-inflammatory macrophages (M1 macrophages) are highly activated, yet their role in the disease remains poorly understood. Previous studies have demonstrated that extracellular vesicles from <jats:italic>C. sinensis<\/jats:italic> (CsEVs) can activate these macrophages, and inhibiting a specific miRNA (Csi-let-7a-5p) in CsEVs (InCsEVs) can reduce this activation. In the present study, liver macrophages in mice were removed using clodronate liposomes (Clodlip). Subsequently, different types of bone marrow-derived macrophages (BMDMs) were adoptively transferred into the mice lacking liver macrophages: untreated (PBS-BMDM), treated with CsEVs (CsEVs-BMDM), treated with a control (ScrCsEVs-BMDM), or treated with InCsEVs (InCsEVs-BMDM). Biliary damages were then evaluated. The results indicated that the transferred macrophages successfully repopulated the mice. CsEVs-BMDM led to significant inflammation and bile duct damage, accompanied by higher levels of inflammatory cytokines (TNF-\u03b1 and IL-1\u03b2). However, when macrophages were treated with InCsEVs, the damage and inflammation were alleviated, and the levels of TNF-\u03b1 and IL-1\u03b2 decreased. These findings suggest that pro-inflammatory macrophages activated by CsEVs, especially through Csi-let-7a-5p, play a crucial role in biliary damage during <jats:italic>C. sinensis<\/jats:italic> infection. Although other immune cells may also be involved, this study emphasizes the significance of pro-inflammatory macrophages in clonorchiasis.<\/jats:p>","DOI":"10.1371\/journal.pntd.0013080","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T17:23:27Z","timestamp":1747157007000},"page":"e0013080","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clonorchis sinensis extracellular vesicles associated with Csi-let-7a-5p activate pro-inflammatory macrophages to induce biliary 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