Diversity and immune dynamics of choroid plexus macrophages are shaped by distinct developmental origins [scRNA-seq steady state]

The choroid plexus, responsible for cerebrospinal fluid production, is vital for brain functions. This organ serves as a crucial interface between the central nervous system and systemic circulation and thus faces constant immunological challenges. While resident macrophages within the choroid plexus provide immunosurveillance, their biological characteristics and immune dynamics remain poorly understood. In this study, we extensively examined the phenotype of choroid plexus macrophages using high-throughput single-cell RNA sequencing, flow cytometry, and imaging techniques. Our data unveiled three distinct macrophage populations within the homeostatic choroid plexus expressing either CD163, MHCII, or CD9. These macrophage subsets exhibited differential input from primitive and definitive hematopoietic waves, different spatial location and relied on distinct factors for survival. Upon neuroinflammation, these cells orchestrated IFN responses producing chemokines for effector CD8 T cells, while microglia predominantly expressed chemokines for B cells. Finally, we present evidence of phenotypically conserved macrophage subsets in the human choroid plexus.