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<p>The obligate intracellular parasite <i>Toxoplasma gondii</i> 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 <i>T. gondii</i> 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 <i>T. gondii</i> disrupts the human BBB and reveals a novel protective role for IFN-γ in mitigating CNS barrier dysfunction.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月25日

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  • Mia C. Somenzi,
  • Kameron T. Bell,
  • Abigail M. Bitters,
  • Collin S. Stratton,
  • Samantha R. Springston,
  • Kamryn E. Zadeii,
  • Rylee J. Anderson,
  • Avery V. Stanley,
  • Daisy Woellner-Santos,
  • Scott G. Canfield,
  • Américo H. López-Yglesias

摘要

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.