Timing and magnitude of type I interferon responses by distinct sensors impact CD8 T cell exhaustion and chronic viral infection

Cell Host Microbe. 2012 Jun 14;11(6):631-42. doi: 10.1016/j.chom.2012.05.003.


Type I interferon (IFN-I) promotes antiviral CD8(+)T cell responses, but the contribution of different IFN-I sources and signaling pathways are ill defined. While plasmacytoid dendritic cells (pDCs) produce IFN-I upon TLR stimulation, IFN-I is induced in most cells by helicases like MDA5. Using acute and chronic lymphocytic choriomeningitis virus (LCMV) infection models, we determined that pDCs transiently produce IFN-I that minimally impacts CD8(+)T cell responses and viral persistence. Rather, MDA5 is the key sensor that induces IFN-I required for CD8(+)T cell responses. In the absence of MDA5, CD8(+)T cell responses to acute infection rely on CD4(+)T cell help, and loss of both CD4(+)T cells and MDA5 results in CD8(+)T cell exhaustion and persistent infection. Chronic LCMV infection rapidly attenuates IFN-I responses, but early administration of exogenous IFN-I rescues CD8(+)T cells, promoting viral clearance. Thus, effective antiviral CD8(+)T cell responses depend on the timing and magnitude of IFN-I production.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • DEAD-box RNA Helicases / metabolism
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Female
  • Immune Tolerance*
  • Interferon Type I / immunology*
  • Interferon-Induced Helicase, IFIH1
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic choriomeningitis virus / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic


  • Interferon Type I
  • Ifih1 protein, mouse
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1