Recombinant Microneme Proteins MIC1 and MIC4 from Toxoplasma gondii Cause Cytotoxic Effects in the Human Jurkat

Igor E L Souza1, Maria-Cristina Roque-Barreira1, Ademilson Panunto-Castelo2

  • 1Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14040-901, SP, Brazil.

Insights

Toxoplasma gondii MIC1 and MIC4 proteins induce apoptosis in human T cells by activating caspases and MAPK pathways. These parasitic lectins

Area of Science:

  • Immunology
  • Parasitology
  • Cell Biology

Background:

  • Toxoplasma gondii causes toxoplasmosis, a significant threat to fetuses and immunocompromised individuals.
  • MIC1 and MIC4 are key T. gondii microneme proteins involved in host cell adhesion via glycan binding.
  • The immunomodulatory and apoptotic effects of MIC1 and MIC4 on human immune cells are not well understood.

Purpose of the Study:

  • To investigate the interaction of recombinant MIC1 (rMIC1) and rMIC4 with Jurkat T lymphocytes.
  • To elucidate the mechanisms by which MIC1 and MIC4 affect human immune cell viability and signaling.

Main Methods:

  • Utilized recombinant MIC1 (rMIC1) and rMIC4.
  • Studied interactions with Jurkat T lymphocytes, a human immune cell model.
  • Assessed cell viability, apoptosis, caspase activation, reactive oxygen species (ROS) production, and MAPK pathway activation.

Main Results:

  • Both rMIC1 and rMIC4 demonstrated carbohydrate-dependent binding to Jurkat cells, with rMIC4 exhibiting competitive binding.
  • rMIC1 and rMIC4 significantly reduced Jurkat cell viability in a time- and dose-dependent manner.
  • Apoptosis was induced via caspase activation (extrinsic and intrinsic pathways), ROS production (NADPH oxidase), and p38/JNK MAPK signaling.

Conclusions:

  • MIC1 and MIC4 directly modulate human T lymphocyte function, inducing apoptosis.
  • These parasitic lectins trigger cellular signaling cascades involving ROS and MAPK pathways.
  • The findings provide mechanistic insights into T. gondii MIC1 and MIC4 interactions with host immune cells.

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