# IFN-γ protects the human blood-brain barrier from Toxoplasma gondii-mediated dysfunction via CCL2 suppression

## TL;DR

This study shows how the parasite Toxoplasma gondii weakens the brain's protective barrier and how IFN-γ helps protect it.

## Contribution

The novel finding is that IFN-γ protects the blood-brain barrier by suppressing CCL2, a newly identified driver of barrier dysfunction.

## Key findings

- Toxoplasma gondii infection causes CCL2 secretion from brain endothelial cells, leading to blood-brain barrier dysfunction.
- IFN-γ reduces CCL2 release and prevents barrier damage in infected cells.
- IFN-γ activates a protective mechanism in brain endothelial cells during infection.

## Abstract

The obligate intracellular parasite Toxoplasma gondii infects nearly one-third of the global population, yet its impact on human blood–brain barrier (BBB) function remains poorly defined. In this study, we use human induced pluripotent stem cell-derived (iPSC) brain-like microvascular endothelial cells (BMECs), a physiologically relevant BBB model, to investigate if T. gondii infection directly compromises barrier integrity. We show that infection induces robust monocyte chemotactic protein-1 (also known as CCL2) secretion from BMECs, and that CCL2 itself serves as a previously unrecognized driver of BBB dysfunction. Notably, interferon-gamma (IFN-γ) limits BMEC-derived CCL2 release and protects against parasite-mediated barrier damage. These findings identify an IFN-γ-dependent, BMEC-intrinsic defense mechanism that helps preserve central nervous system (CNS) integrity during infection. Collectively, this work establishes a mechanistic foundation for understanding how T. gondii disrupts the human BBB and reveals a novel protective role for IFN-γ in mitigating CNS barrier dysfunction.