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Alliance"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:p>Interferon-inducible GTPases, such as immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs), are essential for cell-autonomous immunity against a wide variety of intracellular pathogens including<jats:italic>Toxoplasma<\/jats:italic>. IRGs comprise regulatory and effector subfamily proteins. Regulatory IRGs Irgm1 and Irgm3 play important roles in anti-<jats:italic>Toxoplasma<\/jats:italic>immunity by globally controlling effector IRGs and GBPs. There is a remaining regulatory IRG, called Irgm2, which highly accumulates on parasitophorous vacuole membranes (PVMs). Very little is known about the mechanism of the unique localization on<jats:italic>Toxoplasma<\/jats:italic>PVMs. Here, we show that Irgm2 is important to control parasite killing through recruitment of Gbp1 and Irgb6, which does not require Irgm2 localization at<jats:italic>Toxoplasma<\/jats:italic>PVMs. Ubiquitination of Irgm2 in the cytosol, but not at the PVM, is also important for parasite killing through recruitment of Gbp1 to the PVM. Conversely, PVM ubiquitination and p62\/Sqstm1 loading at later time points post-<jats:italic>Toxoplasma<\/jats:italic>infection require Irgm2 localization at the PVM. Irgm2-deficient mice are highly susceptible to<jats:italic>Toxoplasma<\/jats:italic>infection. Taken together, these data indicate that Irgm2 selectively controls accumulation of anti-<jats:italic>Toxoplasma<\/jats:italic>effectors to the vacuole in a manner dependent or independent on Irgm2 localization at the<jats:italic>Toxoplasma<\/jats:italic>PVM, which mediates parasite killing.<\/jats:p>","DOI":"10.26508\/lsa.202000960","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T19:39:37Z","timestamp":1622662777000},"page":"e202000960","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Cell-autonomous<i>Toxoplasma<\/i>killing program requires Irgm2 but not its microbe vacuolar localization"],"prefix":"10.26508","volume":"4","author":[{"given":"Ariel","family":"Pradipta","sequence":"first","affiliation":[{"name":"Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan"},{"name":"Laboratory of Immunoparasitology, WPI 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