Type I IFN activates border-associated macrophages to drive MHC-I–dependent immune surveillance after stroke

Central nervous system border-associated macrophages (BAMs) reside at the interfaces of the cerebrospinal fluid, the brain parenchyma, and the vasculature, positioning them as key sensors of cerebrovascular injury. We examined the response of BAMs to ischemic stroke using mice engineered to report combined Cx3cr1 and Lyve1 expression. Stroke induced proliferation of embryonically derived BAMs and promoted their acquisition of a pro-inflammatory state along with MHC-I-mediated enhanced antigen presentation capabilities. MHC-I upregulation was driven by the delayed activation of a type-I interferon (IFN-I) program. Although CD8+ T cells were largely bystander-activated after stroke and infiltrated the brain in an antigen-independent manner, BAMs interacted with infiltrating CD8+ T cells in both mouse and human brains. Overall, the study shows that stroke reprograms BAMs into an IFN-I–driven, antigen presenting state that can enhance CD8+ T cell-mediated immune surveillance in the brain.