Differential responses of immune cells to type I interferon contribute to host resistance to viral infection

Cell Host Microbe. 2012 Oct 18;12(4):571-84. doi: 10.1016/j.chom.2012.09.002.


Type I interferons (IFNs) are central to antiviral defense, but how they orchestrate immune cell function is incompletely understood. We determined that IFNs produced during murine cytomegalovirus (MCMV) infection differentially affect dendritic cells (DCs) and natural killer (NK) cells. IFNs induce cell-intrinsic responses in DCs, activating antiproliferative, antiviral, and lymphocyte-activating gene networks, consistent with high activity of the transcription factor STAT1 in these cells. By comparison, NK cells exhibit lower STAT1 expression and reduced IFN responsiveness. Rather, IFNs indirectly affect NK cells by inducing IL-15, which activates the transcription factor E2F and stimulates genes promoting cell expansion. IFN cell-intrinsic responses are necessary in DCs, but not NK cells, for MCMV resistance. Thus, sensitivity to IFN-induced cytokines and differences in IFN receptor signaling program immune cells to mount distinct responses that promote viral control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Flow Cytometry
  • Gene Expression Profiling
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / veterinary
  • Interferon Type I / immunology*
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Muromegalovirus / immunology*
  • Signal Transduction


  • Interferon Type I

Associated data

  • GEO/GSE21491
  • GEO/GSE39555
  • GEO/GSE39556