Microglia are resident immune cells of the CNS and have similar characteristics to peripheral derived macrophages (PdMs). Under normal physiological conditions microglia exclusively tile the brain, with the brain parenchyma completely devoid of PdMs. We recently published a study showing hematopoietic stem cell transplantation (HSCT) with busulfan myeloablation caused microglia to become senescent and decrease to a critical density, which caused extensive PdM brain engraftment. The engrafted PdMs became resident and had similar tiling and surveilling characteristics as the microglia they replaced. Yet, how the host brain recruits PdMs to engraft the parenchyma, where the engrafted PdMs originate, and how/if engrafted PdMs regulate neurons activity is unknown.
We aim to decipher the signaling mechanisms that ultimately shift the brain to become permissive to PdM engraftment.
