IFN-gamma overcomes low responsiveness of myeloid dendritic cells to CpG DNA.
Dendritic cells (DC) are professional APC that have an extraordinary capacity to prime naive T cells. It has been reported that human DC subsets express distinct toll-like receptor (TLR), which influences their function. In mice, we observed that plasmocytoid DC (pDC) express a higher level of TLR9 compared with myeloid DC (mDC) cultured with GM-CSF. However, we demonstrated that stimulation with IFN-gamma is capable of upregulating TLR9 expression in mDC to a level comparable with expression in pDC. Consistent with this observation, IL-12 p40 and IL-6 mRNA expression and IL-12 p70 secretion in response to CpG-oligodeoxynucleotides are enhanced in mDC pretreated with IFN-gamma compared with untreated cells. Therefore, TLR-mediated responses of DC subsets may be influenced not only by signals delivered by pathogens but also by regulatory signals from cytokines such as IFN-gamma.
Uchijima
Masato
M
Department of Microbiology and Immunology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Nagata
Toshi
T
Aoshi
Taiki
T
Koide
Yukio
Y
D000818:Animals; D001853:Bone Marrow; D002478:Cells, Cultured; D018899:CpG Islands; D004269:DNA, Bacterial / Q000276:immunology; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D007109:Immunity; D007371:Interferon-gamma / Q000494:pharmacology*; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000494:pharmacology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics; D051217:Toll-Like Receptor 9; D015854:Up-Regulation / Q000187:drug effects
D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; D021122:Protein Subunits; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D018664:Interleukin-12; D007371:Interferon-gamma