# Recombinant Microneme Proteins MIC1 and MIC4 from Toxoplasma gondii Cause Cytotoxic Effects in the Human Jurkat T-Lymphocyte Cell Line

## TL;DR

This study shows that proteins from the parasite Toxoplasma gondii can harm human immune cells by causing cell death through specific signaling pathways.

## Contribution

The novel finding is that recombinant MIC1 and MIC4 proteins induce apoptosis in Jurkat T-cells via ROS and MAPK pathways.

## Key findings

- rMIC1 and rMIC4 bind Jurkat cells in a carbohydrate-dependent manner, with rMIC4 showing competitive binding.
- Both proteins reduce Jurkat cell viability through caspase activation via extrinsic and intrinsic apoptosis pathways.
- Apoptosis is driven by ROS production via NADPH oxidase and activation of p38 and JNK MAPK pathways.

## 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.