{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T06:31:35Z","timestamp":1771655495546,"version":"3.50.1"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T00:00:00Z","timestamp":1621987200000},"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. Cell Dev. Biol."],"abstract":"<jats:p><jats:italic>Toxoplasma gondii<\/jats:italic> is an intracellular pathogen that exerts its virulence through inhibiting host\u2019s innate immune responses, which is mainly related to the type II interferon (IFN-\u03b3) response. IFN-\u03b3 inducible tripartite motif 21 (TRIM21), an E3 ligase, plays an important role in anti-infection responses against the intracellular pathogens including bacteria, virus, and parasite. We found that <jats:italic>T. gondii<\/jats:italic> virulence factor ROP18 of the type I RH strain (<jats:italic>Tg<\/jats:italic>ROP18<jats:sub>I<\/jats:sub>) interacted with human TRIM21, and promoted the latter\u2019s phosphorylation, which subsequently accelerated TRIM21 degradation through lysosomal pathway. Furthermore, TRIM21 protein level was found to be upregulated during RH and CEP strains of <jats:italic>T. gondii<\/jats:italic> infection. TRIM21 knocking down reduced the ubiquitin labeling on the parasitophorous vacuole membrane (PVM) [which led to parasitophorous vacuole (PV) acidification and death of CEP tachyzoites], and relieved the inhibition of CEP proliferation induced by IFN-\u03b3 in human foreskin fibroblast (HFF) cells which was consistent with the result of TRIM21 overexpression. On the other hand, TRIM21 overexpression enhanced the inhibition of CEP proliferation, and inhibited the binding of I\u03baB-\u03b1 with p65 to activate the IFN-\u03b3-inducible NF-\u03baB pathway, which might be resulted by TRIM21-I\u03baB-\u03b1 interaction. In brief, our research identified that in human cells, IFN-\u03b3-inducible TRIM21 functioned in the innate immune responses against type III <jats:italic>T. gondii<\/jats:italic> infection; however, <jats:italic>Tg<\/jats:italic>ROP18<jats:sub>I<\/jats:sub> promoted TRIM21 phosphorylation, leading to TRIM21 degradation for immune escape in type I strain infection.<\/jats:p>","DOI":"10.3389\/fcell.2021.685913","type":"journal-article","created":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T06:52:08Z","timestamp":1622011928000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Toxoplasma gondii Type-I ROP18 Targeting Human E3 Ligase TRIM21 for Immune Escape"],"prefix":"10.3389","volume":"9","author":[{"given":"Lijie","family":"Yao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liqing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijuan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuizhen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihao","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiating","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjuan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2006","article-title":"A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO\/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response.","volume":"12","author":"Ashida","year":"2010","journal-title":"Nat. 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