IFN-beta modulates the response to TLR stimulation in human DC: involvement of IFN regulatory factor-1 (IRF-1) in IL-27 gene expression

Eur J Immunol. 2007 Dec;37(12):3499-508. doi: 10.1002/eji.200737566.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • B7-2 Antigen / biosynthesis
  • B7-2 Antigen / 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 / metabolism
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / genetics
  • Interleukin-6 / metabolism
  • 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 / metabolism

Substances

  • Antigens, CD
  • B7-2 Antigen
  • CCR7 protein, human
  • CD83 antigen
  • CD86 protein, human
  • IL10 protein, human
  • IL27 protein, human
  • IL6 protein, human
  • Immunoglobulins
  • Interferon Regulatory Factor-1
  • Interleukin-6
  • Interleukins
  • Lipopolysaccharides
  • MYDGF protein, human
  • Membrane Glycoproteins
  • Protein Subunits
  • Receptors, CCR7
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • lipopolysaccharide, Escherichia coli O111 B4
  • Interleukin-10
  • Interleukin-12
  • Interferon-beta