Microglia Plasticity During Health and Disease: An Immunological Perspective

Microglia are macrophages of the central nervous system (CNS) that continuously scrutinize their environment for damage. They colonize the cephalic mesenchyme during embryogenesis and actively shape the developing neuronal network by immune-mediated mechanisms. Upon CNS maturation, microglia drastically change phenotype and function. During health, adult microglia contribute to homeostasis, but also the establishment and resolution of inflammatory conditions. Fulfillment of these distinct tasks requires these long-lived cells to accurately adjust to their changing environment. Deciphering microglia responsiveness to divergent stimuli is central to understanding this cell type and for eventual microglia manipulation to potentially reduce disease burden. Here we discuss new aspects of myeloid cell biology in general with special emphasis on the shifting role of microglia during establishment and protection of CNS integrity.

TrendsMicroglia respond to environmental stimuli, including from surrounding tissue and from systemic inputs. These stimuli impact microglial development and function in both health and disease.The tissue microenvironment, in combination with lineage-specific TFs, shapes the chromatin landscape of microglia and tissue-resident macrophages and drives the selection and usage of enhancers.There is plasticity in the system: adult macrophages can alter their epigenetic landscape when transplanted to a different tissue.Disruption of the intestinal microbiota results in significant alterations in microglial maturation and function in both germ-free mice and on antibiotic treatment of adult mice, indicating that microglia are responsive to continuous input from the intestinal system throughout adulthood.