{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:28:39Z","timestamp":1792456119256,"version":"4.5.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Alveolar echinococcosis (AE) is a life-threatening zoonotic parasitic disease caused by the metacestode stage of <jats:italic>Echinococcus multilocularis<\/jats:italic>, characterized by granulomatous lesions and liver fibrosis. Immune exhaustion is the key mechanism by which <jats:italic>E. multilocularis<\/jats:italic> evades host immune responses and maintains long-term parasitism. Although CD155 is recognized as an immune checkpoint molecule, its specific role and underlying mechanism in AE remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A mouse model of <jats:italic>E. multilocularis<\/jats:italic> infection was used to investigate the role of CD155 in AE progression. Flow cytometry, immunohistochemistry, and immunofluorescence were employed to assess CD155 expression and analyze T-cell function. In addition, liver weight, lesion size, lesion number, inflammation index, collagen deposition (via Masson staining), and stellate cell activation (via \u03b1-SMA immunohistochemistry) were statistically quantified in the CD155 hepatocyte knockout mice. Each experimental group included five mice (<jats:italic>n<\/jats:italic>\u202f=\u202f5).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CD155 expression in hepatocytes was significantly increased\u2014approximately 2-fold compared to Sham controls\u2014and predominantly localized near lesion sites. The infected group showed significantly reduced percentages of functional CD4<jats:sup>+<\/jats:sup>IFN-\u03b3<jats:sup>+<\/jats:sup>, CD4<jats:sup>+<\/jats:sup>CD107a<jats:sup>+<\/jats:sup>, and CD8<jats:sup>+<\/jats:sup>CD107a<jats:sup>+<\/jats:sup> T cells (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05), along with enrichment of exhausted TIGIT<jats:sup>+<\/jats:sup> T cells adjacent to CD155<jats:sup>+<\/jats:sup> hepatocytes. <jats:italic>In vitro<\/jats:italic>, CD155 expression in hepatocytes was upregulated in a dose-dependent manner when co-cultured with metacestode vesicles, reaching 1.5-fold that of the control. Notably, hepatocyte-specific CD155 knockout in infected mice restored CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T-cell function and reduced liver damage, as indicated by decreased lesion burden.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In the <jats:italic>E. multilocularis<\/jats:italic> infection mouse model, excretory\/secretory products from metacestode vesicles upregulated CD155 expression in hepatocytes, contributing to an immunosuppressive microenvironment and T-cell exhaustion. Targeting CD155 reverses this immunosuppression and mitigates hepatic pathology, highlighting CD155 as a promising therapeutic target for AE.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1624387","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:38Z","timestamp":1751347718000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["CD155 as a therapeutic target in alveolar echinococcosis: insights from an Echinococcus multilocularis infection mouse model"],"prefix":"10.3389","volume":"16","author":[{"given":"Xue","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlong","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"L\u00fc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuerganaili","family":"Aji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.3892\/ol.2013.1280","article-title":"Prognostic significance of Cd155 mrna expression in soft tissue sarcomas","volume":"5","author":"Atsumi","year":"2013","journal-title":"Oncol. 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