Abstract
The mechanisms by which neurons respond to inflammatory mediators such as interferons (IFNs) remain largely undefined. We previously showed that the activation and nuclear localization of the core IFN signaling molecule, Stat1, are muted and delayed in primary mouse hippocampal neurons treated with IFN gamma as compared to control mouse embryonic fibroblasts (MEFs). Here, we show that the kinetics of Stat1 and Stat2 activation following type I IFN exposure are also unique in neurons, affecting gene expression and neuronal response. Specifically, despite lower basal expression of many IFN stimulated genes in neurons, basal expression of the type I IFN themselves is significantly higher in primary hippocampal neurons compared to MEF. Elevated homeostatic IFN in neurons is critical and sufficient for early control of viral infection. These data provide further evidence that neurons exploit unique signaling responses to IFNs, and define an important contribution of homeostatic IFN within the CNS. Such differences are likely critical for the ability of neurons to survive a viral challenge.