Type I Interferon Signaling Prevents IL-1β-Driven Lethal Systemic Hyperinflammation during Invasive Bacterial Infection of Soft Tissue

Cell Host Microbe. 2016 Mar 9;19(3):375-87. doi: 10.1016/j.chom.2016.02.003.


Type I interferons (IFN-Is) are fundamental for antiviral immunity, but their role in bacterial infections is contradictory and incompletely described. Streptococcus pyogenes activates IFN-I production in innate immune cells, and IFN-I receptor 1 (Ifnar1)-deficient mice are highly susceptible to S. pyogenes infection. Here we report that IFN-I signaling protects the host against invasive S. pyogenes infection by restricting inflammation-driven damage in distant tissues. Lethality following infection in Ifnar1-deficient mice is caused by systemically exacerbated levels of the proinflammatory cytokine IL-1β. Critical cellular effectors of IFN-I in vivo are LysM+ and CD11c+ myeloid cells, which exhibit suppression of Il1b transcription upon Ifnar1 engagement. These cells are also the major source of IFN-β, which is significantly induced by S. pyogenes 23S rRNA in an Irf5-dependent manner. Our study establishes IL-1β and IFN-I levels as key homeostatic variables of protective, yet tuned, immune responses against severe invasive bacterial infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Interferon Type I / metabolism*
  • Interleukin-1beta / metabolism*
  • Mice
  • Mice, Knockout
  • Signal Transduction*
  • Soft Tissue Infections / immunology*
  • Soft Tissue Infections / pathology*
  • Streptococcal Infections / immunology*
  • Streptococcal Infections / pathology*
  • Survival Analysis


  • Interferon Type I
  • Interleukin-1beta