Microglial Function and Immune Responses in the Central Nervous System

Microglia are the principal immune sentinels of the central nervous system, tasked with surveying the neural environment, clearing debris, sculpting synaptic connections and orchestrating inflammatory reactions. In the steady state, ramified microglia continuously extend and retract processes to sample extracellular signals, phagocytose apoptotic cells and maintain homeostasis. Upon detection of injury, infection or protein aggregates, microglia undergo morphological transformation, upregulate cytokines and chemokines and activate intracellular signalling cascades that can be either protective or detrimental. Phenotypic polarisation spans a spectrum from pro-inflammatory, neurotoxic responses—characterised by tumour necrosis factor-α, interleukin-1β and reactive oxygen species—to anti-inflammatory, pro-regenerative programmes that support tissue repair and neurotrophic support. Key molecular regulators include MAP kinases, inflammasome complexes and transcription factors that integrate signals from damaged cells, pathogen-associated molecular patterns and altered neurotransmitter levels. Dysregulated microglial activation contributes to the pathogenesis of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and psychiatric disorders, while controlled modulation of microglial states offers therapeutic promise for neurodegeneration, injury and cognitive decline.

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Microglial Function and Immune Responses in the Central Nervous System publication trend

The graph below shows the total number of articles in microglial function and immune responses in the central nervous system across all publications each year (not limited to Nature Index journals).

Technical terms

Microglia: Resident immune cells of the CNS that survey the parenchyma, clear debris by phagocytosis and regulate inflammatory responses.

Neuroinflammation: Inflammatory processes within the CNS involving activation of glial cells and release of cytokines, chemokines and reactive species.

NLRP3 inflammasome: A multiprotein cytosolic complex that activates caspase-1, leading to maturation of interleukin-1β and interleukin-18.

p38 MAPK pathway: A mitogen-activated protein kinase signalling cascade that transduces stress and inflammatory signals in microglia.

STAT1: A transcription factor activated by interferons that drives expression of genes involved in immune and inflammatory responses.

Muscarinic acetylcholine receptors (mAChRs): G-protein-coupled receptors responsive to acetylcholine, which modulate microglial activation and cytokine production.

References

1. SDS3 regulates microglial inflammation by modulating the expression of the upstream kinase ASK1 in the p38 MAPK signaling pathway. Inflammation Research (2024).
2. Microglial priming by IFN‐γ involves STAT1‐mediated activation of the NLRP3 inflammasome. CNS Neuroscience & Therapeutics (2024).
3. The Activation of Muscarinic Acetylcholine Receptors Protects against Neuroinflammation in a Mouse Model through Attenuating Microglial Inflammation. International Journal of Molecular Sciences (2024).