{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:31:26Z","timestamp":1783344686497,"version":"3.54.6"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31672543"],"award-info":[{"award-number":["31672543"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Autophagy has been recognized as a bona fide immunological process. Evidence has shown that this process in IFN-\u03b3 stimulated cells controls <jats:italic>Toxoplasma gondii<\/jats:italic> proliferation or eliminates its infection. However, little is known about the effect of <jats:italic>T. gondii<\/jats:italic> infection on the host cell autophagy in the absence of IFN-\u03b3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Multiple autophagy detection methods and CRISPR\/CAS9 technology were used to study <jats:italic>T. gondii<\/jats:italic>-induced autophagy in HeLa and several other mammalian cell lines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we report increased LC3 II, autophagosome-like membrane structures, enhanced autophagic flux, and decreased lysosomes in a range of mammalian cell lines without IFN-\u03b3 treatment after <jats:italic>T. gondii<\/jats:italic> infection. Specifically, disruption of host <jats:italic>atg5<\/jats:italic> (a necessary gene for autophagy) in HeLa cells promoted the intracellular replication of <jats:italic>T. gondii<\/jats:italic>, with the transcript level of <jats:italic>rab11a<\/jats:italic> increased, compared with that in wild-type cells. Further, after <jats:italic>T. gondii<\/jats:italic> infection, the abundance of Rab11A remained stable in wild-type HeLa cells but decreased in <jats:italic>atg5<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mutant. Disruption of <jats:italic>rab11a<\/jats:italic> in the HeLa cells compromised the proliferation of <jats:italic>T. gondii<\/jats:italic>, and increased the transcription of <jats:italic>gra2<\/jats:italic> in the parasite. Compared to the <jats:italic>T. gondii<\/jats:italic> wild-type RH\u2206<jats:italic>ku80<\/jats:italic> strain, the \u2206<jats:italic>gra2<\/jats:italic> mutant induces enhanced host autophagy in HeLa cells, and results in slower replication of the parasite.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Collectively, these results indicate that host cell autophagy can limit <jats:italic>T. gondii<\/jats:italic> proliferation in an IFN-\u03b3 independent manner, possibly by affecting the hijack of host Rab11A-positive vesicles by the parasite which involved TgGRA2. The findings provide novel insights into <jats:italic>T. gondii<\/jats:italic> infection in host cells and toxoplasmosis research.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2022.1052779","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T04:55:26Z","timestamp":1669870526000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Host autophagy limits Toxoplasma gondii proliferation in the absence of IFN-\u03b3 by affecting the hijack of Rab11A-positive vesicles"],"prefix":"10.3389","volume":"13","author":[{"given":"Lingtao","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqiu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxiu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqun","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyin","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aifang","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1128\/EC.00081-14","article-title":"Toxoplasma gondii development of its replicative niche: in its host cell and beyond","volume":"13","author":"Blader","year":"2014","journal-title":"Eukaryot. 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