Related Experiment Video

Updated: May 10, 2026

Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry
10:43

Analysis of Microglia and Monocyte-derived Macrophages from the Central Nervous System by Flow Cytometry

Published on: June 22, 2017

Monocyte-derived macrophages drive neurological tissue damage through mitochondrial reactive oxygen species

Juan Villar-Vesga1, Donatella De Feo1, Pauline Clément1

  • 1Institute of Experimental Immunology, University of Zurich, Zürich, Switzerland.

Science Immunology
|May 8, 2026
PubMed

Insights

Monocyte-derived macrophages (MdMs) produce more reactive oxygen species (ROS) than microglia in multiple sclerosis (MS). Targeting mitochondrial ROS in MdMs reduced disease severity, identifying them as key drivers of neurological damage.

Area of Science:

  • Neuroimmunology
  • Cellular Biology
  • Pathophysiology

Background:

  • Reactive oxygen species (ROS) are implicated in multiple sclerosis (MS) pathogenesis.
  • The specific contributions of distinct mononuclear phagocyte (MP) populations, including microglia and monocyte-derived macrophages, to ROS production and neuroinflammation remain poorly understood.

Purpose of the Study:

  • To delineate the roles of CNS-resident microglia versus CNS-invading monocyte-derived macrophages (MdMs) in ROS production within the central nervous system (CNS).
  • To investigate the impact of modulating ROS production, specifically mitochondrial ROS (mtROS), on disease severity in a preclinical MS model.

Main Methods:

  • Single-cell profiling was employed to analyze ROS production in CNS-resident microglia and infiltrating MdMs.
  • Conditional gene targeting was used to modulate ROS production in specific MP populations.
  • Mitochondria-targeted catalase (mCAT) was expressed in MdMs and microglia to quench mtROS.

Main Results:

  • MdMs exhibited a significantly higher oxidative stress gene signature and produced more ROS compared to microglia.
  • Phagocytic NADPH oxidase 2 was found to be dispensable for neuroinflammation.
  • Targeting mtROS in MdMs, but not microglia, using mCAT ameliorated disease severity in acute neuroinflammation.
  • Core phagocyte functions remained unaltered in mCAT-expressing MdMs.

Conclusions:

  • Monocyte-derived macrophages are the primary source of ROS-mediated oxidative damage in the CNS during MS.
  • Mitochondrial ROS (mtROS) produced by MdMs play a direct neurotoxic role in neuroinflammation.
  • Targeting mtROS in MdMs presents a potential therapeutic strategy for MS.

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