Getting on your last nerve: IFNs and resistance to infection.

Interferons (IFNs) affect almost all nucleated cells and induce transcriptional events that are associated with control of intracellular infections as well as regulatory pathways that influence inflammatory processes. How different hematopoietic and non-hematopoietic cell types interpret these signals is a reflection of cellular context and function. For example, neurons are often viewed as immunologically inert and have muted responses to IFNs. However, because neurons can be targeted by several classes of pathogens, there is a need for these cells to sense infection and respond to IFNs to engage anti-microbial activities. This review discusses the unique features of neuronal IFN signaling, emphasizing how JAK-STAT pathway engagement and downstream induction of interferon-stimulated genes (ISGs) shape intrinsic and extrinsic neuronal anti-pathogen defense.