{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:46:20Z","timestamp":1790405180574,"version":"4.1.0"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"national nature science foundation of china","doi-asserted-by":"crossref","award":["81772225"],"award-info":[{"award-number":["81772225"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"national nature science foundation of china","doi-asserted-by":"crossref","award":["81971969"],"award-info":[{"award-number":["81971969"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the fifth round of three-year public health action plan of shanghai","award":["GWV-10.1-XK13"],"award-info":[{"award-number":["GWV-10.1-XK13"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Schistosomiasis, which is caused by infection with <jats:italic>Schistosoma<\/jats:italic> spp., is characterized by granuloma and fibrosis in response to egg deposition. Pattern recognition receptors are important to sense invading <jats:italic>Schistosoma<\/jats:italic>, triggering an innate immune response, and subsequently shaping adaptive immunity. Cyclic GMP-AMP synthase (cGAS) was identified as a major cytosolic DNA sensor, which catalyzes the formation of cyclic GMP-AMP (cGAMP), a critical second messenger for the activation of the adaptor protein stimulator of interferon genes (STING). The engagement of STING by cGAMP leads to the activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and the subsequent type I interferon (IFN) response. cGAS is suggested to regulate infectious diseases, autoimmune diseases, and cancer. However, the function of cGAS in helminth infection is unclear. In this study, we found that <jats:italic>Cgas<\/jats:italic> deficiency enhanced the survival of mice infected with <jats:italic>S<\/jats:italic>. <jats:italic>japonicum<\/jats:italic> markedly, without affecting the egg load in the liver. Consistently, <jats:italic>Cgas<\/jats:italic> deletion alleviated liver pathological impairment, reduced egg granuloma formation, and decreased fibrosis severity. In contrast, <jats:italic>Sting<\/jats:italic> deletion reduced the formation of egg granulomas markedly, but not liver fibrosis. Notably, <jats:italic>Cgas<\/jats:italic> or <jats:italic>Sting<\/jats:italic> deficiency reduced the production of IFN\u03b2 drastically in mice infected with <jats:italic>S<\/jats:italic>. <jats:italic>japonicum<\/jats:italic>. Intriguingly, intravenous administration of recombinant IFN\u03b2 exacerbated liver damage and promoted egg granuloma formation, without affecting liver fibrosis. Clodronate liposome-mediated depletion of macrophages indicated that macrophages are the major type of cells contributing to the induction of the type I IFN response during schistosome infection. Moreover, cGAS is important for type I IFN production and phosphorylation of TBK1 and IRF3 in response to stimulation with <jats:italic>S<\/jats:italic>. <jats:italic>japonicum<\/jats:italic> egg- or adult worm-derived DNA in macrophages. Our results clarified the immunomodulatory effect of cGAS in the regulation of liver granuloma formation during <jats:italic>S<\/jats:italic>. <jats:italic>japonicum<\/jats:italic> infection, involving sensing schistosome-derived DNA and producing type I IFN. Additionally, we showed that cGAS regulates liver fibrosis in a STING-type I\u2013IFN-independent manner.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010233","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T18:34:01Z","timestamp":1643826841000},"page":"e1010233","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["cGAS exacerbates Schistosoma japonicum infection in a STING-type I IFN-dependent and independent 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