The immune competence of astrocytes is still ill defined, especially their endocytic capacity, a prerequisite for efficient antigen presentation. We show that mannose receptor, a very important conduit for internalization of infectious agents and self antigens, is functionally expressed in the murine CNS. By in vitro assays, astrocytes and microglia were shown to be the prime cells expressing this receptor. Studies on astrocytes demonstrate that its expression and function are inversely regulated by anti-and pro-inflammatory compounds. Downregulation of the mannose receptor by IFN-gamma is concomitant with the induction of the invariant chain, which is also induced by GM-CSF + IL-4. Mannose receptor-expressing astrocytes may thus act as scavenger not only in CNS development but also in defense, against soluble and particulate mannosylated pathogens, presenting fragments thereof at strategic locations in the CNS. These findings unravel a new and putatively very important role of astrocytes in innate immunity and possibly development.