Dendritic Cells and Microglia Have Non-Redundant Functions in the Inflamed Brain with Protective Effects of Type 1 cDCs

Brain CD11c+ cells share features with microglia and dendritic cells (DCs). Sterile inflammation increases brain CD11c+ cells but their phenotype, origin, and functions remain largely unknown. We report that after cerebral ischemia, microglia attract DCs to the inflamed brain and astroglia produce Flt3 ligand supporting development and expansion of CD11c+ cells. CD11c+ cells in the inflamed brain are a complex population derived from proliferating microglia and infiltrating DCs, including a major subset of OX40L+ conventional cDC2, and also cDC1, plasmacytoid and monocyte-derived DCs. Despite sharing certain morphological features and markers, CD11c+ microglia and DCs display differential expression of pattern recognition receptors and chemokine receptors. DCs excel CD11c- and CD11c+ microglia in the capacity to present antigen through MHC I and MHC II. Of note, cDC1s protect from brain injury after ischemia. We thus reveal novel aspects of the dynamics and functions of brain DCs in regulation of inflammation and immunity.