Distinct CpG DNA and polyinosinic-polycytidylic acid double-stranded RNA, respectively, stimulate CD11c- type 2 dendritic cell precursors and CD11c+ dendritic cells to produce type I IFN.
Two classes of nucleic acids, bacterial DNA containing unmethylated CpG motifs and dsRNA in viruses, induce the production of type I IFN that contributes to the immunostimulatory effects of these microbial molecules. Thus, it is important to determine which cells produce type I IFN in response to CpG DNA and dsRNA. CD4(+)CD11c(-) type 2 dendritic cell precursors (pre-DC2) were identified as the main producers of type I IFN in human blood in response to viruses. Here we asked whether pre-DC2 also produce type I IFN in response to CpG DNA and dsRNA. Oligodeoxynucleotides containing particular palindromic CpG motifs induced pre-DC2, but not CD11c(+) blood DC or monocytes, to produce IFN-alpha. In contrast, a synthetic dsRNA, polyinosinic polycytidylic-acid, induced CD11c(+) DC, but not pre-DC2 or monocytes, to produce IFN-alphabeta. These data indicate that CpG DNA and polyinosinic-polycytidylic acid stimulate different types of cells to produce type I IFN and that it is important to select oligodeoxynucleotides containing particular CpG motifs to induce pre-DC2 to produce type I IFN, which may play a key role in the strong adjuvant effects of CpG DNA.
Kadowaki
N
N
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA. kadowaki@kuhp.kyoto-u.ac.jp
Antonenko
S
S
Liu
Y J
YJ
D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis*; D007369:Interferon Inducers / Q000494:pharmacology*; D007370:Interferon Type I / Q000096:biosynthesis*; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011070:Poly I-C / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
C408982:CPG-oligonucleotide; D016167:Integrin alphaXbeta2; D007369:Interferon Inducers; D007370:Interferon Type I; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D012330:RNA, Double-Stranded; D018664:Interleukin-12; D016899:Interferon-beta; D011070:Poly I-C