Fig. 2. Location of brain-resident macrophages.

Microglia are the major innate immune cells in the brain parenchyma that are exclusively derived from yolk sac (YS)-derived embryonic precursor cells. All other brain-resident macrophages, including meningeal, perivascular, and choroid plexus macrophages, which originate from both YS- and fetal liver (FL)-derived progenitor cells, are located at the brain-circulation interface. Brain-resident macrophages maintain their population by self-renewal, whereas only the choroid plexus macrophages receive input from the circulating hematopoietic stem cell (HSC)-derived progenitors. Cardiac and intestinal macrophages also originate from the HSC-derived progenitor cells. Peripheral tissue macrophages in the epidermis and heart are derived from embryonic precursors. FL-derived precursor cells are committed to forming Kupffer cells in the liver and alveolar macrophages in the lung. CSF, cerebrospinal fluid; CNS, central nervous system.