Neurons produce type I interferon during viral encephalitis

Abstract

Type I interferons, also referred to as IFN-α/β, form the first line of defense against viral infections. Major IFN-α/β producers in the periphery are the plasmacytoid dendritic cells (pDCs). Constitutive expression of the IFN regulatory factor (IRF)-7 enables pDCs to rapidly synthesize large amounts of IFN-α/β after viral infection. In the central nervous system (CNS), pDCs are considered to be absent from the parenchyma, and little is known about the cells producing IFN-α/β. The study presented here aimed to identify the cells producing IFN-α/β in the CNS in vivo after infection by neurotropic viruses such as Theiler9s virus and La Crosse virus. No cells with high constitutive expression of IRF-7 were detected in the CNS of uninfected mice, suggesting the absence of cells equivalent to pDCs. Upon viral infection, IFN-β and some subtypes of IFN-α, but not IFN-ε or IFN-κ, were transcriptionally up-regulated. IFN-α/β was predominantly produced by scattered parenchymal cells and much less by cells of inflammatory foci. Interestingly, in addition to some macrophages and ependymal cells, neurons turned out to be important producers of both IFN-α and IFN-β. However, only 3% of the infected neurons produced IFN-α/β, suggesting that some restriction to IFN-α/β production existed in these cells. All CNS cell types analyzed, including neurons, were able to respond to type I IFN by producing Mx or IRF-7. Our data show that, in vivo, neurons take an active part to the antiviral defense by being both IFN-α/β producers and responders.