Production of IFNβ by Conventional Dendritic Cells after Stimulation with Viral Compounds and IFNβ-Independent IFNAR1-Signaling Pathways are Associated with Aggravation of Polymicrobial Sepsis

Int J Mol Sci. 2019 Sep 7;20(18):4410. doi: 10.3390/ijms20184410.


Viral infections are associated with increased incidence of severe sepsis. Particularly during the early stages, type I interferons (IFNs) are known mediators of detrimental effects. However, the functional role of early interferon β (IFNβ) and its cellular source during sepsis in the context of preexisting viral infections has not been defined. Using the colon ascendens stent peritonitis (CASP) model, we demonstrate that IFNβ-/- and type I IFN receptor (IFNAR1)-/- mice were less susceptible to sepsis after pre-stimulation with the viral mimetic poly(I:C). Wild type (WT) mice treated with poly(I:C) exhibited altered expression patterns of TNF and IL-12p40 during CASP which were dependent on IFNβ or IFNAR1, suggesting a mechanism for the increased sepsis susceptibility of WT mice. Using a double cytokine reporter mouse model, we present novel data on the simultaneous expression of IFNβ and IL-12p40 on a single cell level during polymicrobial sepsis in vivo. Conventional dendritic cells (cDCs) were identified as primary source of IFNβ and the protective cytokine IL-12p40 after CASP surgery irrespective of poly(I:C) pre-stimulation. These data demonstrated that if polymicrobial sepsis is preceded by a viral infection, IFNβ and IL-12p40 are expressed by polyfunctional cDCs suggesting that these cells can play both detrimental and beneficial roles during sepsis development.

Keywords: IL-12; cytokine reporter mouse model; dendritic cells; immunotherapy; interferon β; sepsis; type I interferons; viral infection.

MeSH terms

  • Animals
  • Coinfection / blood
  • Coinfection / immunology*
  • Coinfection / virology
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Female
  • Gene Knockout Techniques
  • Interferon-beta / genetics*
  • Interferon-beta / metabolism
  • Interleukin-12 Subunit p40 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Poly I-C / administration & dosage*
  • Poly I-C / immunology
  • Receptor, Interferon alpha-beta / genetics*
  • Receptor, Interferon alpha-beta / metabolism
  • Sepsis / immunology*
  • Sepsis / virology
  • Signal Transduction


  • Ifnar1 protein, mouse
  • Interleukin-12 Subunit p40
  • Receptor, Interferon alpha-beta
  • Interferon-beta
  • Poly I-C