IFN-beta modulates the response to TLR stimulation in human DC: involvement of IFN regulatory factor-1 (IRF-1) in IL-27 gene expression.
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.
Remoli
Maria Elena
ME
Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Gafa
Valérie
V
Giacomini
Elena
E
Severa
Martina
M
Lande
Roberto
R
Coccia
Eliana M
EM
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics; D050856:Interferon Regulatory Factor-1 / Q000502:physiology*; D016899:Interferon-beta / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D021122:Protein Subunits; D054400:Receptors, CCR7 / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D007136:Immunoglobulins; D050856:Interferon Regulatory Factor-1; D016899:Interferon-beta; D016753:Interleukin-10; D018664:Interleukin-12; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D054400:Receptors, CCR7; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C515370:CCR7 protein, human; C497964:CD86 protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; C464565:MYDGF protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C440499:lipopolysaccharide, Escherichia coli O111 B4