Activation with CpG-A and CpG-B Oligonucleotides Reveals Two Distinct Regulatory Pathways of Type I IFN Synthesis in Human Plasmacytoid Dendritic Cells
- 1 May 2003
- journal article
- research article
- Published by The American Association of Immunologists
- Vol. 170 (9), 4465-4474
- https://doi.org/10.4049/jimmunol.170.9.4465
Abstract
Two different CpG oligonucleotides (ODN) were used to study the regulation of type I IFN in human plasmacytoid dendritic cells (PDC): ODN 2216, a CpG-A ODN, known to induce high amounts of IFN-α in PDC, and ODN 2006, a CpG-B ODN, which is potent at stimulating B cells. CpG-A ODN showed higher and prolonged kinetics of type I IFN production compared with that of CpG-B ODN. In contrast, CpG-B ODN was more active than CpG-A ODN in stimulating IL-8 production and increasing costimulatory and Ag-presenting molecules, suggesting that CpG-A and CpG-B trigger distinct regulatory pathways in PDC. Indeed, CpG-A ODN, but not CpG-B ODN, activated the type I IFNR-mediated autocrine feedback loop. PDC were found to express high constitutive levels of IFN regulatory factor (IRF)7. IRF7 and STAT1, but not IRF3, were equally up-regulated by both CpG-A and CpG-B. CD40 ligand synergistically increased CpG-B-induced IFN-α independent of the IFNR but did not affect CpG-B-induced IFN-β. In conclusion, our studies provide evidence for the existence of two distinct regulatory pathways of type I IFN synthesis in human PDC, one dependent on and one independent of the IFNR-mediated feedback loop. The alternate use of these pathways is based on the type of stimulus rather than the quantity of IFN-αβ available to trigger the IFNR. Constitutive expression of IRF7 and the ability to produce considerable amounts of IFN-α independent of the IFNR seem to represent characteristic features of PDC.Keywords
This publication has 47 references indexed in Scilit:
- Type I Interferon Production by Plasmacytoid Dendritic Cells and Monocytes Is Triggered by Viruses, but the Level of Production Is Controlled by Distinct CytokinesJournal of Interferon & Cytokine Research, 2002
- Interferon-α and Interleukin-12 Are Induced Differentially by Toll-like Receptor 7 Ligands in Human Blood Dendritic Cell SubsetsThe Journal of Experimental Medicine, 2002
- CpG Motifs in Bacterial DNA and Their Immune EffectsAnnual Review of Immunology, 2002
- The Development of Murine Plasmacytoid Dendritic Cell Precursors Is Differentially Regulated by FLT3-ligand and Granulocyte/Macrophage Colony-Stimulating FactorThe Journal of Experimental Medicine, 2002
- Small anti-viral compounds activate immune cells via the TLR7 MyD88–dependent signaling pathwayNature Immunology, 2002
- Distinct CpG oligonucleotide sequences activate human γ δ T cells via interferon-α/-βEuropean Journal of Immunology, 2001
- Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12European Journal of Immunology, 2001
- Subsets of Human Dendritic Cell Precursors Express Different Toll-like Receptors and Respond to Different Microbial AntigensThe Journal of Experimental Medicine, 2001
- Identification of CpG oligonucleotide sequences with high induction of IFN-α/β in plasmacytoid dendritic cellsEuropean Journal of Immunology, 2001
- STATs and Gene RegulationScience, 1997