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IFNα enhances the production of IL-6 by human neutrophils activated via TLR8
- Source :
- Scientific Reports
- Publication Year :
- 2016
- Publisher :
- Nature Publishing Group, 2016.
-
Abstract
- Recently, we reported that human neutrophils produce biologically active amounts of IL-6 when incubated with agonists activating TLR8, a receptor recognizing viral single strand RNA. In this study, we demonstrate that IFNα, a cytokine that modulates the early innate immune responses toward viral and bacterial infections, potently enhances the production of IL-6 in neutrophils stimulated with R848, a TLR8 agonist. We also show that such an effect is not caused by an IFNα-dependent induction of TLR7 and its consequent co-activation with TLR8 in response to R848, but, rather, it is substantially mediated by an increased production and release of endogenous TNFα. The latter cytokine, in an autocrine manner, leads to an augmented synthesis of the IkBζ co-activator and an enhanced recruitment of the C/EBPβ transcription factor to the IL-6 promoter. Moreover, we show that neutrophils from SLE patients with active disease state, hence displaying an IFN-induced gene expression signature, produce increased amounts of both IL-6 and TNFα in response to R848 as compared to healthy donors. Altogether, data uncover novel effects that type I IFN exerts in TLR8-activated neutrophils, which therefore enlarge our knowledge on the various biological actions which type I IFN orchestrates during infectious and autoimmune diseases.
- Subjects :
- 0301 basic medicine
Adult
Cell Survival
Neutrophils
medicine.medical_treatment
SLE
IFNalpha
Article
03 medical and health sciences
Young Adult
0302 clinical medicine
medicine
Humans
Lupus Erythematosus, Systemic
Interleukin 6
Receptor
Autocrine signalling
Promoter Regions, Genetic
TLR8
Aged
IL-6
Multidisciplinary
Innate immune system
biology
business.industry
Interleukin-6
Tumor Necrosis Factor-alpha
CCAAT-Enhancer-Binding Protein-beta
Gene Expression Profiling
neutrophils
Imidazoles
Interferon-alpha
TLR7
Middle Aged
030104 developmental biology
Cytokine
Gene Expression Regulation
Toll-Like Receptor 7
Genetic Loci
Toll-Like Receptor 8
Immunology
biology.protein
Tumor necrosis factor alpha
Female
business
030215 immunology
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....ebab7d086bbb06753d1279eb945f3302
- Full Text :
- https://doi.org/10.1038/srep19674