Activated Brain Endothelial Cells Cross-Present Malaria Antigen

In the murine model of cerebral malaria caused by p. berghei anka (pba),parasite-specific cd8+t cells directly induce pathology and have long been hypothesized to kill brain endothelial cells that have internalized pba antigen. we previously reported that brain microvessel fragments from infected mice cross-present pba epitopes,using reporter cells transduced with epitope-specific t cell receptors. here,we confirm that endothelial cells are the population responsible for cross-presentation in vivo,not pericytes or microglia. pba antigen cross-presentation by primary brain endothelial cells in vitro confers susceptibility to killing by cd8+t cells from infected mice. ifnγ stimulation is required for brain endothelial cross-presentation in vivo and in vitro,which occurs by a proteasome- and tap-dependent mechanism. parasite strains that do not induce cerebral malaria were phagocytosed and cross-presented less efficiently than pba in vitro. the main source of antigen appears to be free merozoites,which were avidly phagocytosed. a human brain endothelial cell line also phagocytosed p. falciparum merozoites. besides being the first demonstration of cross-presentation by brain endothelial cells,our results suggest that interfering with merozoite phagocytosis or antigen processing may be effective strategies for cerebral malaria intervention. © 2015 howland et al.