title: Activation of type I interferon-dependent genes characterizes the "core response" induced by CpG DNA.
abstract: Synthetic ODNs expressing CpG motifs trigger an innate immune response via TLR9. pDCs are major effectors of this response. Two structurally distinct classes of CpG ODNs have been identified that differentially activate pDCs. "K" ODNs trigger the production of TNF-α and IL-6, whereas "D" ODNs preferentially induce the secretion of IFN-α. As K and D ODNs have distinct therapeutic effects, knowledge of their shared and sequence-specific activity is of considerable importance. This work uses the CAL-1 human pDC line to analyze the effect of CpG stimulation on gene expression. Genes up-regulated by both K and D ODNs (n=92) were largely dependent on type I IFN signaling and characterized functionally by antiviral activity. K ODNs induced a short-term increase in IFN-α/β production and uniquely up-regulated genes that supported antibacterial responses. In contrast, D ODNs triggered a persistent increase in IFN-α/β production and uniquely up-regulated genes associated with metabolic functions. Thus, the core functionality of human pDCs mediated by TLR9 ligation rests on a type I IFN response that differs from the response induced by the structural elements unique to specific classes of ODNs.
authors: Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
authors: Folkert
authors: F
authors: Steinhagen
authors: Corinna
authors: C
authors: Meyer
authors: Debra
authors: D
authors: Tross
authors: Mayda
authors: M
authors: Gursel
authors: Takahiro
authors: T
authors: Maeda
authors: Sven
authors: S
authors: Klaschik
authors: Dennis M
authors: DM
authors: Klinman
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000032:analysis / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D007370:Interferon Type I; D009838:Oligodeoxyribonucleotides; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9