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However, the Toxoplasma effector proteins involved remain unknown. Herein, we identified that T. gondii macrophage migration inhibitory factor (TgMIF) is a critical pathogenic factor of liver injury in acute toxoplasmosis mouse model induced by a less virulent strain, which is widely prevalent in humans. We show that TgMIF is a novel activator of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in hepatocytes, resulting in subsequent pyroptosis. Furthermore, T. gondii promotes the TgMIF-dependent infiltration of Ly6Chi proinflammatory macrophages to release cytokines, leading to hepatocyte apoptosis. Although the intense inflammation induced by TgMIF inhibits the proliferation of intracellular parasites, it results in fatal liver damage. In contrast, parasites with TgMIF gene deletion significantly alleviate liver injury and prolong mice survival. The discovery of novel Toxoplasma virulence factor may expedite the development of human toxoplasmosis control strategies.<\/jats:p>","DOI":"10.1093\/infdis\/jiac422","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T09:00:08Z","timestamp":1666688408000},"page":"1417-1427","source":"Crossref","is-referenced-by-count":11,"title":["<i>Tg<\/i>MIF Promotes Hepatocyte Pyroptosis and Recruitment of Proinflammatory Macrophages During Severe Liver Injury in Acute Toxoplasmosis"],"prefix":"10.1093","volume":"227","author":[{"given":"Nan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University , Hefei , China"},{"name":"The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University , Hefei , China"},{"name":"The Provincial Key Laboratory of Zoonoses of High Institutions in Anhui, Anhui Medical University , Hefei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University , Hefei , China"},{"name":"The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University , Hefei , China"},{"name":"The Provincial Key Laboratory of Zoonoses of High Institutions in Anhui, Anhui Medical University , Hefei , China"},{"name":"School of Nursing, Anhui Medical University , Hefei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University , Hefei , China"},{"name":"The Research Center for Infectious Diseases, School of Basic Medical Sciences, Anhui Medical University , Hefei , 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