Novel Characterization of Monocyte-Derived Cell Populations in the Meninges and Choroid Plexus and Their Rates of Replenishment in Bone Marrow Chimeric Mice

The mouse dura mater, pia mater, and choroid plexus contain resident macrophages and dendritic cells (DCs). These cells participate in immune surveillance, phagocytosis of cellular debris, uptake of antigens from the surrounding cerebrospinal fluid and immune regulation in many pathologic processes. We used Cx(3)cr1(gfp) knock-in, CD11c-eYFP transgenic and bone marrow chimeric mice to characterize the phenotype, density and replenishment rate of monocyte-derived cells in the meninges and choroid plexus and to assess the role of the chemokine receptor CX(3)CR1 on their number and tissue distribution. Iba-1(+) major histocompatibility complex (MHC) Class II+ CD169(+) CD68(+) macrophages and CD11c(+) putative DCs were identified in meningeal and choroid plexus whole mounts. Comparison of homozygous and heterozygous Cx(3)cr1(gfp) mice did not reveal CX(3)CR1-dependancy on density, distribution or phenotype of monocyte-derived cells. In turnover studies, wild type lethally irradiated mice were reconstituted with Cx(3)cr1/(gfp)-positive bone marrow and were analyzed at 3 days, 1, 2, 4 and 8 weeks after transplantation. There was a rapid replenishment of CX(3)CR1(gfp)-positive cells in the dura mater (at 4 weeks) and the choroid plexus was fully reconstituted by 8 weeks. These data provide the foundation for future studies on the role of resident macrophages and DCs in conditions such as meningitis, autoimmune inflammatory disease and in therapies involving irradiation and hematopoietic or stem cell transplantation.