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Peer-reviewedCC BYCellular and Molecular Immunology

Microglia and neuroinflammation: function, heterogeneity, and crosstalk

  • Shuai Zong1
  • Xiaolin Cui1
  • Shuang Wu2
  • Zhiming Lu3
  1. 1Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
  2. 2Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
  3. 3Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. [email protected]
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Abstract

Microglia, the resident innate immune cells of the central nervous system (CNS), are indispensable for maintaining brain homeostasis, conducting immune surveillance, and responding to injury. Recent single-cell sequencing studies have revealed that activated microglia exhibit a spectrum of activation states that extend well beyond the classical proinflammatory/anti-inflammatory dichotomy, encompassing distinct subpopulations such as disease-associated microglia (DAMs), termed interferon-responsive microglia (IRMs), and lipid-droplet-accumulating microglia (LDAMs). Their remarkable plasticity enables microglia to adopt dual functional roles-either neuroprotective or neurotoxic-depending on the context of neuroinflammatory disease progression. Furthermore, microglia do not act in isolation but serve as central communicators within a dynamic cellular network of the CNS, interacting with neurons, astrocytes, oligodendrocytes, and peripheral immune cells to regulate processes such as synaptic pruning, inflammatory amplification, and myelin integrity and repair. This review provides a comprehensive overview of microglial origin, development, and classification, as well as the dynamic spectrum of microglial cellular states. Furthermore, we discuss the classical and latest mechanisms of microglia-mediated neuroinflammation and focus on the crosstalk between microglia and other cells of the CNS. The hub position of microglia within neuroinflammatory networks, together with their unique cellular characteristics, may unlock a promising frontier for the development of precision therapeutic strategies against neuroinflammatory disorders.

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Cite

BibTeXRIS
BibTeX
@article{zong2026microglia,
  title = {{Microglia and neuroinflammation: function, heterogeneity, and crosstalk}},
  author = {Shuai Zong and Xiaolin Cui and Shuang Wu and Zhiming Lu},
  journal = {Cellular and Molecular Immunology},
  year = {2026},
  month = jun,
  doi = {10.1038/s41423-026-01438-3},
  url = {https://doi.org/10.1038/s41423-026-01438-3},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Microglia and neuroinflammation: function, heterogeneity, and crosstalk
AU  - Shuai Zong
AU  - Xiaolin Cui
AU  - Shuang Wu
AU  - Zhiming Lu
PY  - 2026
DA  - 2026/06/04
JO  - Cellular and Molecular Immunology
DO  - 10.1038/s41423-026-01438-3
UR  - https://doi.org/10.1038/s41423-026-01438-3
AB  - Microglia, the resident innate immune cells of the central nervous system (CNS), are indispensable for maintaining brain homeostasis, conducting immune surveillance, and responding to injury. Recent single-cell sequencing studies have revealed that activated microglia exhibit a spectrum of activation states that extend well beyond the classical proinflammatory/anti-inflammatory dichotomy, encompassing distinct subpopulations such as disease-associated microglia (DAMs), termed interferon-responsive microglia (IRMs), and lipid-droplet-accumulating microglia (LDAMs). Their remarkable plasticity enables microglia to adopt dual functional roles-either neuroprotective or neurotoxic-depending on the context of neuroinflammatory disease progression. Furthermore, microglia do not act in isolation but serve as central communicators within a dynamic cellular network of the CNS, interacting with neurons, astrocytes, oligodendrocytes, and peripheral immune cells to regulate processes such as synaptic pruning, inflammatory amplification, and myelin integrity and repair. This review provides a comprehensive overview of microglial origin, development, and classification, as well as the dynamic spectrum of microglial cellular states. Furthermore, we discuss the classical and latest mechanisms of microglia-mediated neuroinflammation and focus on the crosstalk between microglia and other cells of the CNS. The hub position of microglia within neuroinflammatory networks, together with their unique cellular characteristics, may unlock a promising frontier for the development of precision therapeutic strategies against neuroinflammatory disorders.
SN  - 1672-7681
SN  - 2042-0226
ER  -