Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / biosynthesis
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Antigens, CD / genetics
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B7-2 Antigen / biosynthesis
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B7-2 Antigen / genetics
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CD83 Antigen
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Cells, Cultured / drug effects
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Cells, Cultured / metabolism
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Dendritic Cells / drug effects*
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Dendritic Cells / metabolism
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Gene Expression Regulation / drug effects
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Humans
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Immunoglobulins / biosynthesis
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Immunoglobulins / genetics
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Interferon Regulatory Factor-1 / physiology*
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Interferon-beta / pharmacology*
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Interleukin-10 / metabolism
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Interleukin-12 / biosynthesis
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Interleukin-12 / genetics
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Interleukin-6 / metabolism
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Interleukins / biosynthesis*
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Interleukins / genetics
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Lipopolysaccharides / pharmacology
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Protein Subunits
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Receptors, CCR7 / biosynthesis
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Receptors, CCR7 / genetics
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Signal Transduction / physiology
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Toll-Like Receptor 2 / physiology*
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Toll-Like Receptor 4 / physiology*
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antigens, CD
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B7-2 Antigen
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CCR7 protein, human
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CD86 protein, human
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IL10 protein, human
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IL6 protein, human
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Immunoglobulins
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Interferon Regulatory Factor-1
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Interleukin-6
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Interleukins
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Lipopolysaccharides
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MYDGF protein, human
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Membrane Glycoproteins
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Protein Subunits
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Receptors, CCR7
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TLR2 protein, human
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TLR4 protein, human
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Toll-Like Receptor 2
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Toll-Like Receptor 4
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Tumor Necrosis Factor-alpha
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lipopolysaccharide, Escherichia coli O111 B4
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Interleukin-10
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Interleukin-12
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Interferon-beta