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 MHCI and MHCII. Of note, cDC1s protect from brain injury after ischemia. We thus reveal aspects of the dynamics and functions of brain DCs in the regulation of inflammation and immunity. [Display omitted] •Microglia and DCs have distinct transcriptional profiles and functions in ischemia•DCs excel over microglia in antigen presentation upon brain ischemia•Ischemic microglia release chemokines attracting DCs, in particular cDC1 through CCR1•cDC1 exert beneficial effects in brain ischemia CD11c+ dendritic cells infiltrate the brain after ischemic injury and share some features with microglia. Gallizioli et al. show that dendritic cells exhibit a transcriptional profile different from microglia and excel in antigen presentation. Microglia attract different DC subsets via chemokines, especially cDC1 that exert beneficial functions in cerebral ischemia.