{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:56:12Z","timestamp":1790607372140,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0014035","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000}}],"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472313"],"award-info":[{"award-number":["82472313"]}],"id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Anhui Provincial Health and Medical Research Project","award":["AHWJ2023A30013"],"award-info":[{"award-number":["AHWJ2023A30013"]}]},{"name":"Basic and Clinical Research Enhancement Program of Anhui Medical University","award":["2023xkjT040"],"award-info":[{"award-number":["2023xkjT040"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    is an opportunistic protozoan parasite that can establish latent infections in humans, causing toxoplasmosis in immunocompromised individuals. Type I interferons (IFN-I), particularly IFN-\u03b2, are critical for controlling\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    infection, but the parasite has evolved various strategies to manipulate the host immune response. Interferon regulatory factor 3 (IRF3) is a key transcription factor that regulates the expression of antiviral genes, including IFN-I and ISGs. Unlike IFN-\u03b2, IRF3-activated ISG56 can enhance\n                    <jats:italic>T. gondii<\/jats:italic>\n                    proliferation. Furthermore, STAT6 activation has also been reported to promote the proliferation of\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    . In this study, we found that GRA3 is highly expressed in the less virulent ME49 strain. Furthermore, we discovered that GRA3 interacted with STING to activate the cGAS\/STING pathway. This interaction promotes STING oligomerization and the nuclear translocation of phosphorylated-IRF3, which in turn enhances IFN-\u03b2 production. GRA3 in ME49 tachyzoites promoted both IRF3-mediated ISG56 expression and STAT6 phosphorylation, thereby enhancing the proliferation of these less virulent parasites. Interestingly, GRA3 enhances parasite proliferation\n                    <jats:italic>via<\/jats:italic>\n                    a mechanism mediated by ISG56 and STAT6, rather than by IFN-\u03b2. This study highlights how less virulent strains modulate host immunity to promote\n                    <jats:italic>T. gondii<\/jats:italic>\n                    survival and replication, establish latent infections, and ultimately achieve widespread dissemination in humans.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0014035","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T18:41:36Z","timestamp":1771526496000},"page":"e0014035","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Toxoplasma gondii GRA3 activates interferon-stimulated genes and STAT6 by the cGAS-STING pathway to promote parasite 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