Gateways for myeloid cell entry into the central nervous system

Resident myeloid cells are the main constituents of the healthy central nervous system's (CNS) immune compartment. They usually seed the developing CNS prior to birth, remain there lifelong, and essentially contribute to neuronal network formation and establishment of physiology. While CNS anatomy is optimized for efficient connectivity, function, and maintenance of neuronal cells, distinct structures facilitate selective postnatal immune cell trafficking, including entry of myeloid cells. These myeloid gateways become active upon physiological need, during aging, or in pathologies. As a consequence, individual CNS compartments show variable accessibility to short-living circulating myeloid cells derived from postnatal bone marrow sources. Here, we summarize our current view of myeloid cell trafficking into the healthy CNS, spanning embryogenesis to physiological aging and highlight recent discoveries of novel routes. A precise understanding of the anatomical and molecular properties of myeloid gateways is essential to develop targeted cell therapies to treat myeloid-cell-driven CNS perturbations.