Microglial states revisited: from homeostasis to disease.
Level 5 - mechanism / opinion, no new human data
Narrative review and mechanistic framework synthesis without primary empirical human data or systematic review methodology.
PubMed 42477453 · doi:10.1038/s41583-026-01066-w
What was done
This narrative review synthesizes advances in single-cell and single-nucleus transcriptomics, chromatin accessibility profiling, and spatial multi-omics regarding microglia in the central nervous system parencyhma. It outlines a multidimensional state framework replacing binary 'resting versus activated' or 'M1 versus M2' models and examines microglial transcriptomic shifts across development, homeostasis, neurodegeneration, demyelination, and infection.
What was found
The abstract provides no quantitative data or numerical findings. It conceptualizes microglial phenotypes as a multidimensional state space shaped by development, region, sex, age, genotype, and environmental challenges. It describes latent or 'hidden' microglial states that appear homeostatic at baseline but are altered by innate immune training or tolerance following prior challenges (such as sepsis or viral infection), influencing variability in disease trajectories.
Why it matters
It provides an updated framework for interpreting single-cell and spatial omics data in neuroimmunology, moving field standards away from oversimplified binary models toward multi-factor, state-resolved biomarkers and interventions.
Limits
As a narrative review, it presents conceptual models and synthesizes prior literature without primary empirical data, quantitative effect estimates, or systematic study selection. The clinical translation and cross-species fidelity of these multidimensional microglial states remain to be established.
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- context Systemic inflammation causes microglia to polarize into a pro-inflammatory M1 phenotype that releases damaging cytokines, creating a feed-forward cycle that activates further microglia.