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IFN-beta modulates the response to TLR stimulation in human DC: involvement of IFN regulatory factor-1 (IRF-1) in IL-27 gene expression.
European Journal of Immunology
Date de publication
Type I IFN are cytokines which play a central role in host resistance to viral or microbial infections and are important components linking innate and adaptive immunity. We and others have previously demonstrated that the production of IFN-beta by DC following bacterial infections or TLR triggering influences, in an autocrine manner, their maturation. In this study, we investigated whether IFN-beta release modulates the phenotype of the immature DC and their response to a subsequent TLR stimulation. The induction of CD86, HLA-DR, CD38 and B7H1 and the absence of CCR7 and CD83 expression upon IFN-beta treatment suggest that IFN-beta-primed DC remain at the site of infection acquiring an activated phenotype. These results prompted us to investigate the response of IFN-beta-primed DC to TLR stimulation. While IFN-beta pretreatment increases slightly the expression of maturation markers in TLR2- or TLR4-stimulated DC, it is able to modulate selectively the secretion of inflammatory and immuno-regulating cytokines. Interestingly, IL-27p28 subunit was induced by IFN-beta alone or during LPS-induced maturation of DC in a type I IFN-dependent manner through IFN regulatory factor-1 (IRF-1) activation. Taken together, our results shed light on the capacity of IFN-beta to finely tune DC response to invading pathogens.
Antigens, CD/biosynthesis, Antigens, CD/genetics, Antigens, CD86/biosynthesis, Antigens, CD86/genetics, Cells, Cultured/drug effects, Cells, Cultured/metabolism, Dendritic Cells/drug effects, Dendritic Cells/metabolism, Gene Expression Regulation/drug effects, Humans, Immunoglobulins/biosynthesis, Immunoglobulins/genetics, Interferon Regulatory Factor-1/physiology, Interferon-beta/pharmacology, Interleukin-10/secretion, Interleukin-12/biosynthesis, Interleukin-12/genetics, Interleukin-6/secretion, Interleukins/biosynthesis, Interleukins/genetics, Lipopolysaccharides/pharmacology, Membrane Glycoproteins/biosynthesis, Membrane Glycoproteins/genetics, Protein Subunits, Receptors, CCR7/biosynthesis, Receptors, CCR7/genetics, Signal Transduction/physiology, Toll-Like Receptor 2/physiology, Toll-Like Receptor 4/physiology, Tumor Necrosis Factor-alpha/secretion
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