Mapping the Plasticity of Morphology, Molecular Properties and Function in Mouse Primary Microglia

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Microglia, the brain's immune cells, exhibit diverse functions but their phenotypic plasticity is poorly understood.
• Understanding microglial responses to different stimuli is crucial for brain homeostasis and disease.

Purpose of the Study:

• To investigate the plasticity of microglial phenotypes induced by interferon-gamma (IFN-γ), interleukin-4 (IL-4), and interleukin-10 (IL-10).
• To compare the resulting phenotypes regarding morphology, proliferation, phagocytosis, and neurotoxicity.

Main Methods:

• Primary mouse microglia were stimulated with IFN-γ, IL-4, or IL-10.
• RNA sequencing identified differentially expressed genes.
• Morphology, proliferation, phagocytosis, and neurotoxicity were assessed.

Main Results:

• IFN-γ induced an "immunodefensive" phenotype (iNOS, TNF-α) with high plasticity, proliferation, and neurotoxicity.
• IL-4 induced a "neuroimmunoregulatory" phenotype (Arg-1, YM-1) with moderate plasticity.
• IL-10 induced an "immunosuppressive" phenotype (TGF-β, IL-10) with low plasticity and inhibited inflammation.

Conclusions:

• IFN-γ, IL-4, and IL-10 induce distinct microglial phenotypes with varying plasticity.
• IFN-γ-induced microglia plasticity may aid CNS inflammation repair.
• IL-10-induced immunosuppression reduces microglial plasticity, potentially protecting the brain from immune overactivation.