Type 1 interferons (IFN-α and IFN-β) help defend against viruses through the activation of various protective innate immune pathways. A more controversial idea is that these cytokines also regulate IFN-γ, the type 2 interferon responsible for directing the cell-mediated arm of the adaptive immune response. Nguyen et al. now provide direct evidence that, IFN-α, as well as interleukin 12 (IL-12), can activate the IFN-γ-dependent response to viral infection in mice. However, this process required activation of the signal transducer and activator of transcription 4 (STAT4), which is also the primary target of IL-12. This finding refocuses the role of type-1 IFNs in controlling adaptive, as well as innate, immune responses to pathogens. For information about the canonical signaling pathways activated by interferons, see the Connections Maps [Interferon γ Pathway and the Type 1 Interferon (α/β) Pathway] by Aaronson and Horvath.
K. B. Nguyen, W. T. Watford, R. Salomon, S. R. Hofmann, G. C. Pien, A. Morinobu, M. Gadina, J. J. O'Shea, C. A. Biron, Critical role for STAT4 activation by type 1 interferons in the interferon-γ response to viral infection. Science 297, 2063-2066 (2002). [Abstract] [Full Text]
D. Aaronson, C. M. Horvath, Interferon γ Pathway. Science's STKE (Connections Map as seen September 2002), http://stke.sciencemag.org/cgi/cm/CMP_9590. [Pathway]
D. Aaronson, C. M. Horvath, Type 1 Interferon (α/β) Pathway. Science's STKE (Connections Map as seen September 2002), http://stke.sciencemag.org/cgi/cm/CMP_8390. [Pathway]