Central Nervous System Macrophages in Health and Disease

The central nervous system (CNS) has a unique set of macrophages that seed the tissue early during embryonic development. Microglia reside in the parenchyma, and border-associated macrophages are present in border regions, including the meninges, perivascular spaces, and choroid plexus. CNS-resident macrophages support brain homeostasis during development and steady state. In the diseased brain, however, the immune landscape is altered, with phenotypic and transcriptional changes in resident macrophages and the invasion of blood-borne monocytes, which differentiate into monocyte-derived macrophages upon entering the CNS. In this review, we focus on the fate and function of the macrophage compartment in health, neurodegenerative conditions such as amyloidosis, and neuroinflammation as observed in multiple sclerosis and infection. We discuss our current understanding that monocyte-derived macrophages contribute to neuropathology whereas native macrophages play a neuroprotective role in disease.