{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:04:28Z","timestamp":1792613068744,"version":"4.5.0"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"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. Immunol."],"abstract":"<jats:p>Toxoplasmosis is a prevalent parasitic disease caused by<jats:italic>Toxoplasma gondii<\/jats:italic>(<jats:italic>T. gondii<\/jats:italic>). Under the control of the host immune system,<jats:italic>T. gondii<\/jats:italic>persists as latent bradyzoite cysts. Immunosuppression leads to their reactivation, a potentially life-threatening condition. Interferon-gamma (IFN-\u03b3) controls the different stages of toxoplasmosis. Here, we addressed the role of the parasite surface antigen P18, belonging to the Surface-Antigen 1 (SAG-1) Related Sequence (SRS) family, in a cyst-forming strain. Deletion of<jats:italic>P18<\/jats:italic>gene (KO<jats:italic>P18<\/jats:italic>) impaired the invasion of parasites in macrophages and IFN-\u03b3-mediated activation of macrophages further reduced the invasion capacity of this KO, as compared to WT strain. Mice infected by KO<jats:italic>P18<\/jats:italic>, showed a marked decrease in virulence during acute toxoplasmosis. This was consequent to less parasitemia, accompanied by a substantial recruitment of dendritic cells, macrophages and natural killer cells (NK). Furthermore, KO<jats:italic>P18<\/jats:italic>resulted in a higher number of bradyzoite cysts, and a stronger inflammatory response. A prolonged survival of mice was observed upon immunosuppression of KO<jats:italic>P18<\/jats:italic>infected BALB\/c mice or upon oral infection of Severe Combined Immunodeficiency (SCID) mice, with intact macrophages and natural killer (NK) cells. In stark contrast, oral infection of NSG (NOD\/Shi-scid\/IL-2R\u03b3null) mice, defective in macrophages and NK cells, with<jats:italic>KO P18<\/jats:italic>, was as lethal as that of the control strain showing that the conversion from bradyzoites to tachyzoites is intact and, suggesting a role of P18 in the response to host IFN-\u03b3. Collectively, these data demonstrate a role for P18 surface antigen in the invasion of macrophages and in the virulence of the parasite, during acute and chronic toxoplasmosis.<\/jats:p>","DOI":"10.3389\/fimmu.2021.643292","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T06:15:22Z","timestamp":1624860922000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["P18 (SRS35\/TgSAG4) Plays a Role in the Invasion and Virulence of Toxoplasma gondii"],"prefix":"10.3389","volume":"12","author":[{"given":"Maguy","family":"Hamie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadim","family":"Tawil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"El 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