The Journal of immunology (1950), 2003-03, Vol.170 (6), p.3059-3064
2003
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- Autor(en) / Beteiligte
- Titel
- The Roles of Toll-Like Receptor 9, MyD88, and DNA-Dependent Protein Kinase Catalytic Subunit in the Effects of Two Distinct CpG DNAs on Dendritic Cell Subsets
- Ist Teil von
- The Journal of immunology (1950), 2003-03, Vol.170 (6), p.3059-3064
- Ort / Verlag
- United States: Am Assoc Immnol
- Erscheinungsjahr
- 2003
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Oligodeoxynucleotides containing unmethylated CpG motifs (CpG DNAs) can function as powerful immune adjuvants by activating APC. Compared with conventional phosphorothioate-backbone CpG DNAs, another type of CpG DNAs, called an A or D type (A/D-type), possesses higher ability to induce IFN-alpha production. Conventional CpG DNAs can exert their activity through Toll-like receptor 9 (TLR9) signaling, which depends on a cytoplasmic adapter, MyD88. However, it remains unknown how A/D-type CpG DNAs exhibit their immunostimulatory function. In this study we have investigated murine dendritic cell (DC) responses to these two distinct CpG DNAs. Not only splenic, but also in vitro bone marrow-derived, DCs could produce larger amounts of IFN-alpha in response to A/D-type CpG DNAs compared with conventional CpG DNAs. This IFN-alpha production was mainly due to the B220(+) DC subset. On the other hand, the B220(-) DC subset responded similarly to both CpG DNAs in terms of costimulatory molecule up-regulation and IL-12 induction. IFN-alpha, but not IL-12, induction was dependent on type I IFN. However, all activities of both CpG DNAs were abolished in TLR9- and MyD88-, but were retained in DNA-PKcs-deficient DCs. This study demonstrates that the TLR9-MyD88 signaling pathway is essential for all DC responses to both types of CpG DNAs.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-1767eISSN: 1550-6606DOI: 10.4049/jimmunol.170.6.3059Titel-ID: cdi_proquest_miscellaneous_73077083
- Format
- –
- Schlagworte
- Adaptor Proteins, Signal Transducing, Adjuvants, Immunologic - pharmacology, Animals, Antigens, Differentiation - genetics, Antigens, Differentiation - physiology, Blotting, Northern, Catalytic Domain - genetics, Catalytic Domain - physiology, CD11c Antigen - biosynthesis, CpG Islands - physiology, Cytokines - biosynthesis, Dendritic Cells - immunology, Dendritic Cells - metabolism, DNA, Bacterial - pharmacology, DNA-Activated Protein Kinase, DNA-Binding Proteins - biosynthesis, DNA-Binding Proteins - deficiency, DNA-Binding Proteins - genetics, DNA-Binding Proteins - physiology, Interferon Regulatory Factor-7, Interferon-alpha - biosynthesis, Leukocyte Common Antigens - biosynthesis, Mice, Mice, Inbred C57BL, Mice, Knockout, Myeloid Differentiation Factor 88, Nuclear Proteins, Oligodeoxyribonucleotides - classification, Oligodeoxyribonucleotides - pharmacology, Protein-Serine-Threonine Kinases - deficiency, Protein-Serine-Threonine Kinases - genetics, Protein-Serine-Threonine Kinases - physiology, Receptors, Cell Surface - deficiency, Receptors, Cell Surface - genetics, Receptors, Cell Surface - physiology, Receptors, Immunologic - deficiency, Receptors, Immunologic - genetics, Receptors, Immunologic - physiology, RNA, Messenger - biosynthesis, Spleen - cytology, Spleen - immunology, Spleen - metabolism, Toll-Like Receptor 9