Oligodendroglia are limited in type I interferon induction and responsiveness in vivo

Type I interferons (IFN alpha/beta) provide a primary defense against infection. Nevertheless, the dynamics of IFN alpha/beta induction and responsiveness by central nervous system (CNS) resident cells in vivo in response to viral infections are poorly understood. Mice were infected with a neurotropic coronavirus with tropism for oligodendroglia and microglia to probe innate antiviral responses during acute encephalomyelitis. Expression of genes associated with the IFN alpha/beta pathways was monitored in microglia and oligodendroglia purified from naive and infected mice by fluorescent activated cell sorting. Compared with microglia, oligodendroglia were characterized by low basal expression of mRNA encoding viral RNA sensing pattern recognition receptors (PRRs), IFN alpha/beta receptor chains, interferon sensitive genes (ISG), as well as kinases and transcription factors critical in IFN alpha/beta signaling. Although PRRs and ISGs were upregulated by infection in both cell types, the repertoire and absolute mRNA levels were more limited in oligodendroglia. Furthermore, although oligodendroglia harbored higher levels of viral RNA compared with microglia, Ifn alpha/beta was only induced in microglia. Stimulation with the double stranded RNA analogue poly I:C also failed to induce Ifn alpha/beta in oligodendroglia, and resulted in reduced and delayed induction of ISGs compared with microglia. The limited antiviral response by oligodendroglia was associated with a high threshold for upregulation of Ikke and Irf7 transcripts, both central to amplifying IFN alpha/beta responses. Overall, these data reveal that oligodendroglia from the adult CNS are poor sensors of viral infection and suggest they require exogenous IFN alpha/beta to establish an antiviral state. (c) 2012 Wiley Periodicals, Inc.