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.

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.

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