Human monocyte-derived dendritic cells express TLR9 and react directly to the CpG-A oligonucleotide D19.
Oligodeoxynucleotides (ODNs) containing unmethylated CpG exhibit their immunostimulatory activities by binding to TLR. Here, we show that human monocyte-derived dendritic cells (moDC) contain TLR9 protein, surprisingly, in amounts comparable with plasmacytoid DC (pDC). Immature moDC but not mature moDC nor monocytes captured CpG-ODNs. moDC stimulation with the CpG-A ODN D19 up-regulated CD83, CD86, and HLA-DR. Without CD40 ligand costimulation, full maturation was not achieved. D19-stimulated moDC primed allogeneic CD4(+)-T cells for proliferation and differentiation into IFN-gamma-secreting Th1 cells. Neither IL-12 nor IL-6 or TNF-alpha was involved. Microarray analysis pointed to a participation of Type I IFNs. In fact, D19-stimulated moDC secreted considerable amounts of IFN-alpha. This indicates that moDC themselves sense viral and bacterial DNA and do not need help from pDC.
Hoene
Victoria
V
Institute of Molecular Biology and Bioinformatics, Charité-CBF, Arnimallee 22, 14195 Berlin, Germany.
Peiser
Matthias
M
Wanner
Reinhard
R
D015703:Antigens, CD / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D018899:CpG Islands / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004269:DNA, Bacterial / Q000276:immunology*; D004279:DNA, Viral / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D008024:Ligands; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology*
D015703:Antigens, CD; D016207:Cytokines; D004269:DNA, Bacterial; D004279:DNA, Viral; D008024:Ligands; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9