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- Title
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.
- Authors
Howe, Magdalena; Bauer, Jens; Schulze, Anja; Kropp, Sonja; Locksley, Richard M.; Alferink, Judith; Weighardt, Heike; Scheu, Stefanie
- Abstract
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.
- Subjects
DENDRITIC cells; TYPE I interferons; VIRUS diseases; INTERFERON receptors; SEPSIS
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 18, p4410
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20184410