Interferon-β (IFN-β) is a key component of cellular innate immunity in mammals and forms the first line of defense during viral infection by inducing an antiviral state in responsive cells. In vitro studies showed that almost all nucleated cells are able to produce IFN-β to various extents, but information about the in vivo source of IFN-β remains incomplete. The major producers of IFN in the periphery are plasmacytoid dendritic cells (pDC) which are mainly present in the blood and spleen of mammals. However, because classical immune cells, including pDCs, are usually not present in the brain, other cell types must be responsible for the synthesis of IFN in this organ.
By applying immunohistochemistry and by using conditional reporter mice that express firefly luciferase under control of the IFN-β promoter in either all or only distinct cell types, we found that astrocytes are the main producers of IFN-β after infection of the brain with diverse neurotropic viruses, including La Crosse virus, rabies virus and Theiler's murine encephalomyelitis virus. Surprisingly, however, astrocytes showed no clear signs of infection with these viruses. Therefore, we aimed at identifying the triggers which are necessary to induce IFN-β synthesis in brain astrocytes under these conditions. By employing different knockout mouse strains we could show that sensing via RIG-I-like receptors is necessary for IFN-β production in the virus-infected brain, suggesting that non-productive infection of astrocytes represents a crucial trigger.