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Mechanisms and environmental factors shaping the ecosystem of brain macrophages

Silvia Penati1, Simone Brioschi1, Zhangying Cai1

  • 1Department of Pathology and Immunology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, United States.

Frontiers in Immunology
|February 10, 2025
PubMed

Insights

Brain macrophages, including microglia and border-associated macrophages (BAMs), have distinct roles in brain health. This review explores their development, diversity, and the molecular factors influencing their specialized functions.

Area of Science:

  • Neuroimmunology
  • Developmental Biology
  • Cell Biology

Background:

  • Brain macrophages comprise microglia (parenchyma) and border-associated macrophages (BAMs) (extra-parenchymal).
  • These distinct cell populations are critical for brain homeostasis and immune surveillance.
  • Despite originating from common progenitors, microglia and BAMs exhibit unique phenotypes and functions shaped by their microenvironments.

Purpose of the Study:

  • To review the ontogeny, phenotypic diversity, and environmental factors influencing brain macrophage populations.
  • To highlight current knowledge and research gaps regarding the molecular and epigenetic regulation of microglia and BAMs.
  • To compare findings from human and mouse studies and suggest future research directions.

Main Methods:

  • Literature review synthesizing current research on brain macrophage development and function.
  • Comparative analysis of data from human and mouse studies.
  • Identification of key molecular and epigenetic mechanisms governing brain macrophage differentiation and specialization.

Main Results:

  • Microglia and BAMs, though originating from the same source, diverge developmentally and exhibit distinct characteristics.
  • Specific molecular and epigenetic programs dictate the specialized functions of each brain macrophage population.
  • Human and mouse brain macrophage systems show both conserved and divergent features.

Conclusions:

  • Understanding the developmental trajectories and functional specializations of brain macrophages is crucial for comprehending brain physiology.
  • Further research into the molecular underpinnings of brain macrophage development and function is needed.
  • Investigating brain macrophage-environment interactions will illuminate their roles in health and disease.
Keywords:
border-associated-macrophagesbrain developmentbrain macrophagesmicrogliaontogenyyolk sac

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