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Macrophage invasion into the Drosophila brain requires JAK/STAT-dependent MMP activation in the blood-brain barrier

Bente Winkler1, Dominik Funke1, Christian Klämbt1

  • 1Institut für Neuro- und Verhaltensbiologie, Universität Münster, Münster, Germany.

Plos Biology
|February 20, 2025
PubMed

Insights

Neuroinflammation triggers immune cell invasion into the brain by activating the JAK/STAT pathway, which remodels the extracellular matrix. This study reveals conserved mechanisms of immune cell entry into the nervous system.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • The blood-brain barrier normally protects the central nervous system from peripheral immune cells.
  • Immune cell entry into the brain during neuroinflammation can cause detrimental effects.
  • Mechanisms controlling immune cell invasion through extracellular matrix barriers are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms of peripheral immune cell invasion into the brain using Drosophila melanogaster as a model.
  • To investigate the role of cytokine signaling and extracellular matrix remodeling in immune cell brain entry.

Main Methods:

  • Induction of neuroinflammation in Drosophila melanogaster.
  • Analysis of gene expression in glial cells of the blood-brain barrier.
  • Assessment of extracellular matrix remodeling via matrix metalloproteinase activity.
  • Observation of immune cell invasion into the fly brain.

Main Results:

  • Neuroinflammation induces Unpaired cytokine expression, activating the JAK/STAT signaling pathway in glial cells.
  • Activated JAK/STAT signaling leads to the expression of matrix metalloproteinases.
  • Matrix metalloproteinases remodel the extracellular matrix surrounding the fly brain.
  • Remodeling facilitates the invasion of peripheral immune cells into the brain.

Conclusions:

  • The study identifies a conserved pathway involving cytokines and JAK/STAT signaling in immune cell invasion of the nervous system.
  • Drosophila serves as a valuable model for studying neuroinflammation and immune cell trafficking.
  • Findings contribute to understanding the molecular basis of immune cell entry into the brain, relevant to both invertebrates and vertebrates.

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