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- Title
TgMIF Promotes Hepatocyte Pyroptosis and Recruitment of Proinflammatory Macrophages During Severe Liver Injury in Acute Toxoplasmosis.
- Authors
Zhou, Nan; Chen, Ying; Wang, Jie; An, Ran; Cai, Haijian; Liu, Shutong; Yao, Lei; Tang, Yuewen; Chen, Lijian; Du, Jian
- Abstract
Liver injury is a common complication during infection of Toxoplasma gondii. However, the Toxoplasma effector proteins involved remain unknown. Herein, we identified that T. gondii macrophage migration inhibitory factor (Tg MIF) 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 Tg MIF 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 Tg MIF-dependent infiltration of Ly6Chi proinflammatory macrophages to release cytokines, leading to hepatocyte apoptosis. Although the intense inflammation induced by Tg MIF inhibits the proliferation of intracellular parasites, it results in fatal liver damage. In contrast, parasites with Tg MIF 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.
- Subjects
MACROPHAGE migration inhibitory factor; LIVER injuries; PYROPTOSIS; TOXOPLASMOSIS; TRYPANOSOMA cruzi; MACROPHAGES
- Publication
Journal of Infectious Diseases, 2023, Vol 227, Issue 12, p1417
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jiac422