Microglial cell origin and phenotypes in health and disease

In the central nervous system, microglia have important roles in maintaining tissue homeostasis and responding to infection and injury.Microglia in the brain parenchyma originate from primitive macrophages in the yolk sac and form a population that is distinct from bone marrow-derived macrophages.Microglia can exhibit distinct phenotypes depending on context. These include a quiescent phenotype under normal conditions, a 'classically activated' phenotype in the setting of infection and injury, and an 'alternatively activated' phenotype that is associated with brain tumours.A mild form of a classically activated microglial cell phenotype is frequently observed in the context of chronic neurodegenerative diseases and may be associated with the production of neurotoxic mediators.Alternatively activated microglia are associated with gliomas and are characterized by an immunosuppressive phenotype and the production of mediators that support tumour invasion.Mechanisms that maintain a quiescent phenotype under normal conditions and promote the resolution of classical activation states are regulated by cell–cell communication with neurons and other glial cells, by anti-inflammatory cytokines and by endogenous hormones that are generated locally within the CNS and act by regulating nuclear hormone receptors.