Are “Resting†Microglia More “M2�

Over the last decade, the concept and nomenclature of microglial phenotype polarization has been carried over from the peripheral macrophage literature. However, it is not entirely correct to view these two cell types as overlapping. Microglia, although related to macrophages, have several differences and their own unique repertoire of features. In particular, microglia arise from a distinct early yolk sac progenitor population and therefore have different developmental origins than macrophages (1). Furthermore, once in the central nervous system (CNS), microglia are maintained through local self-renewal (2). Under normal conditions, there is no infiltration of peripheral macrophages (3). Microglia also maintain expression profiles distinct from peripheral macrophages (4). This demonstrates that microglia are not simply macrophages that have migrated into the brain; rather, they are a distinct cell type.