{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:46:53Z","timestamp":1789501613113,"version":"build-2803163510"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI001017"],"award-info":[{"award-number":["AI001017"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>The infection competence of the protozoan pathogen<jats:italic>Toxoplasma gondii<\/jats:italic>is critically dependent on the parasite\u2019s ability to inactivate the host complement system.<jats:italic>Toxoplasma<\/jats:italic>actively resists complement-mediated killing in non-immune serum by recruiting host-derived complement regulatory proteins C4BP and Factor H (FH) to the parasite surface to inactivate surface-bound C3 and limit formation of the C5b-9 membrane attack complex (MAC). While decreased complement activation on the parasite surface certainly protects<jats:italic>Toxoplasma<\/jats:italic>from immediate lysis, the biological effector functions of C3 split products C3b and C3a are maintained, which includes opsonization of the parasite for phagocytosis and potent immunomodulatory effects that promote pro-inflammatory responses and alters mucosal defenses during infection, respectively. In this review, we discuss how complement regulation by<jats:italic>Toxoplasma<\/jats:italic>controls parasite burden systemically but drives exacerbated immune responses locally in the gut of genetically susceptible C57BL\/6J mice. In effect,<jats:italic>Toxoplasma<\/jats:italic>has evolved to strike a balance with the complement system, by inactivating complement to protect the parasite from immediate serum killing, it generates sufficient C3 catabolites that signal through their cognate receptors to stimulate protective immunity. This regulation ultimately controls tachyzoite proliferation and promotes host survival, parasite persistence, and transmissibility to new hosts.<\/jats:p>","DOI":"10.3389\/fcimb.2021.634610","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T04:58:37Z","timestamp":1613969917000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["A Protective and Pathogenic Role for Complement During Acute Toxoplasma gondii Infection"],"prefix":"10.3389","volume":"11","author":[{"given":"Patricia M.","family":"Sikorski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra G.","family":"Commodaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Grigg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1056\/NEJM199005103221903","article-title":"Enhanced Local Production of Complement Components in the Small Intestines of Patients with Crohn\u2019s Disease","volume":"322","author":"Ahrenstedt","year":"1990","journal-title":"New Engl. 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