Abstract

Type I interferons (IFNα/β) provide a primary defense against infection. Nevertheless, the dynamics of IFNα/β 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 IFNα/β pathways was monitored in microglia and oligodendroglia purified from naïve 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), IFNα/β receptor chains, interferon sensitive genes (ISG), as well as kinases and transcription factors critical in IFNα/β 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, Ifnα/β was only induced in microglia. Stimulation with the double stranded RNA analogue poly I:C also failed to induce Ifnα/β 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 Ikkε and Irf7 transcripts, both central to amplifying IFNα/β responses. Overall, these data reveal that oligodendroglia from the adult CNS are poor sensors of viral infection and suggest they require exogenous IFNα/β to establish an antiviral state.

Links

Publisher Full Text

Authors

Kapil P, Butchi NB, Stohlman SA, Bergmann CC

Institution

Department of Neurosciences, NC-30, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Source

Glia 60:10 2012 Oct pg 1555-66

MeSH

Animals
Calmodulin-Binding Proteins
DEAD-box RNA Helicases
Encephalomyelitis
Flow Cytometry
Gene Expression Regulation
Green Fluorescent Proteins
Interferon Inducers
Interferon Type I
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microglia
Myelin Proteolipid Protein
Oligodendroglia
Poly I-C
RNA, Messenger
Signal Transduction
Viral Proteins

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22736486