{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:18:37Z","timestamp":1784269117320,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012790","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000}}],"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province","award":["IMMDL202105"],"award-info":[{"award-number":["IMMDL202105"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Schistosomiasis is characterized by egg-induced hepatic granulomas and subsequent fibrosis. Monocyte-derived macrophages play critical and plastic roles in the progression and regression of liver fibrosis, adopting different polarization phenotypes. Mammalian STE20-like protein kinase 1 (MST1), a serine\/threonine kinase, has been established to act as a negative regulator of macrophage-associated inflammation. However, the specific role of MST1 in <jats:italic>Schistosoma<\/jats:italic>-induced liver fibrosis has not been fully understood. In this study, we demonstrate that macrophage MST1 functions as an inhibitor of inflammation and fibrosis following infection with <jats:italic>Schistosoma japonicum (S<\/jats:italic>. <jats:italic>japonicum)<\/jats:italic>. Mice with macrophages-specific <jats:italic>Mst1<\/jats:italic> knockout (termed <jats:italic>Mst1<\/jats:italic><jats:sup><jats:italic>\u25b3M\/\u25b3M<\/jats:italic><\/jats:sup>) mice developed exacerbated liver pathology, characterized by larger egg-induced granulomas, and increased fibrosis post infection. This was accompanied by enhanced production of proinflammatory cytokines (IL1B, IL6, IL23, TNFA <jats:italic>and<\/jats:italic> TGFB) and a shift in macrophage phenotype towards Ly6C<jats:sup>high<\/jats:sup>. Mechanistically, MST1 activation by soluble egg antigen (SEA) promoted PPAR\u03b3-mediated CD36 expression, enhancing phagocytosis and consequently upregulation of fibrolytic genes such as <jats:italic>Arg1<\/jats:italic> and <jats:italic>Mmps<\/jats:italic>. Conversely, MST1 deletion leads to up-regulation of pro-inflammatory genes instead of fibrolytic genes in macrophages, accompanied by decreased expression of CD36 and impaired phagocytosis. Furthermore, the ablation of MST1 enhances NF-\u03baB activation in <jats:italic>S<\/jats:italic>. <jats:italic>japonicum<\/jats:italic>-infected and SEA-stimulated macrophages, resulting in increased production of proinflammatory cytokines. Overall, our data identified MST1 as a novel regulator for egg-induced liver fibrosis via modulation of macrophage function and phenotype by CD36-mediated phagocytosis and suppression of NF-\u03baB pathway.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012790","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T18:55:29Z","timestamp":1734634529000},"page":"e1012790","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Macrophage MST1 protects against schistosomiasis-induced liver fibrosis by promoting the PPAR\u03b3-CD36 pathway and suppressing NF-\u03baB signaling"],"prefix":"10.1371","volume":"20","author":[{"given":"Jianyang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunhao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Sui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5147-2054","authenticated-orcid":true,"given":"Yuxia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"issue":"12","key":"ppat.1012790.ref001","doi-asserted-by":"crossref","first-page":"e1010064","DOI":"10.1371\/journal.ppat.1010064","article-title":"Schistosome immunomodulators.","volume":"17","author":"S Acharya","year":"2021","journal-title":"PLoS Pathog"},{"issue":"5","key":"ppat.1012790.ref002","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1017\/S0031182023000021","article-title":"Immunological mechanisms involved in macrophage activation and polarization in schistosomiasis","volume":"150","author":"ICL Lic\u00e1","year":"2023","journal-title":"Parasitology"},{"issue":"3","key":"ppat.1012790.ref003","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41575-020-00372-7","article-title":"Molecular and cellular mechanisms of liver fibrosis and its regression","volume":"18","author":"T Kisseleva","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"1","key":"ppat.1012790.ref004","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/nri.2017.90","article-title":"3rd, Wilson MS, Wynn TA. 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