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Published on: January 27, 2021
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.
Abstract:
Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis, a potentially devastating disease to fetuses and immunocompromised individuals. Among its microneme proteins, MIC1 and MIC4 play crucial roles in host-parasite interactions, facilitating adhesion by binding glycans on host cells. Beyond these roles, these lectins have been implicated in modulating immune responses and inducing apoptosis, but their effects on human immune cells remain unclear. Here, we investigated the interaction of recombinant MIC1 (rMIC1) and rMIC4 with Jurkat T lymphocytes, a human immune cell model. Both lectins bound Jurkat cells in a carbohydrate-dependent manner, with rMIC4 showing competitive binding over rMIC1. Importantly, we observed that rMIC1 and rMIC4 reduced Jurkat cell viability in a time- and dose-dependent manner, inducing apoptosis through caspase activation by extrinsic and intrinsic pathways. The apoptosis was driven by reactive oxygen species production via the NADPH oxidase complex and the activation of p38 and JNK MAPK signaling pathways, emphasizing the ability of these lectins to modulate cellular signaling cascades. This study offers insights into the mechanisms involved in MIC1 and MIC4 interactions with immune cells.
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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