Intercellular Communication Is Key for Protective IFN/ Signaling During Viral Central Nervous System Infection

A variety of viruses can induce central nervous system (CNS) infections and neurological diseases, although the incidence is rare. Similar to peripheral infections, IFN/ induction and signaling constitutes a first line of defense to limit virus dissemination. However, CNS-resident cells differ widely in their repertoire and magnitude of both basal and inducible components in the IFN/ pathway. While microglia as resident myeloid cells have been implicated as prominent sentinels of CNS invading pathogens or insults, astrocytes are emerging as key responders to many neurotropic RNA virus infections. Focusing on RNA viruses, this review discusses the role of astrocytes as IFN/ inducers and responders and touches on the role of IFN/ receptor signaling in regulating myeloid cell activation and IFN responsiveness. A summary picture emerges implicating IFN/ not only as key in establishing the classical antiviral state, but also orchestrating cell mobility and IFN-mediated effector functions.