Related Experiment Video
Updated: Jul 26, 2026

Toxoplasma gondii Cyst Wall Formation in Activated Bone Marrow-derived Macrophages and Bradyzoite Conditions
Published on: August 12, 2010
TgMIF Promotes Hepatocyte Pyroptosis and Recruitment of Proinflammatory Macrophages During Severe Liver Injury in
Nan Zhou1,2,3, Ying Chen1,2,3,4, Jie Wang1,2,3
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
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 (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.
Insights
Toxoplasma gondii infection causes liver injury via the TgMIF protein, which activates the NLRP3 inflammasome. Deleting TgMIF reduces liver damage and prolongs survival in mice, offering new control strategies for toxoplasmosis.
Area of Science:
- Immunology
- Infectious Diseases
- Hepatology
Background:
- Liver injury is a frequent complication of Toxoplasma gondii infection.
- The specific effector proteins responsible for this liver damage are not well understood.
Purpose of the Study:
- To identify Toxoplasma gondii effector proteins involved in liver injury.
- To elucidate the mechanism by which these proteins cause pathogenesis.
Main Methods:
- Utilized a mouse model of acute toxoplasmosis with a prevalent, less virulent T. gondii strain.
- Investigated the role of T. gondii macrophage migration inhibitory factor (TgMIF) in liver pathogenesis.
- Assessed inflammasome activation (NLRP3), pyroptosis, and hepatocyte apoptosis.
- Examined macrophage infiltration and cytokine release.
- Compared wild-type and TgMIF-deleted parasite strains.
Main Results:
- TgMIF was identified as a critical pathogenic factor in T. gondii-induced liver injury.
- TgMIF activates the NLRP3 inflammasome in hepatocytes, leading to pyroptosis.
- TgMIF promotes the infiltration of proinflammatory macrophages, exacerbating hepatocyte apoptosis.
- TgMIF deletion significantly reduced liver injury and improved mouse survival.
- While TgMIF-induced inflammation inhibited parasite proliferation, it caused fatal liver damage.
Conclusions:
- TgMIF is a novel virulence factor of T. gondii that drives liver injury through NLRP3 inflammasome activation and pyroptosis.
- TgMIF-mediated inflammation contributes to severe liver damage, despite potentially limiting parasite growth.
- Targeting TgMIF presents a potential strategy for developing new treatments for human toxoplasmosis.
More Related Videos
11:21Forward Genetics Screens Using Macrophages to Identify Toxoplasma gondii Genes Important for Resistance to IFN-γ-Dependent Cell Autonomous Immunity
Published on: March 12, 2015
09:44Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
Related Concept Videos
Toxoplasmosis
Chronic Inflammation: Introduction
Cirrhosis II: Pathophysiology
Acute Pancreatitis II: Pathophysiology