title: Contribution of interferon-beta to the immune activation induced by double-stranded DNA.
abstract: Introducing double-stranded DNA (dsDNA) into the cytoplasm of macrophages and dendritic cells triggers the activation of these professional antigen-presenting cells (APCs). This process is characterized by the up-regulation of costimulatory molecules and the production of various cytokines, chemokines, and antibacterial/viral factors. Current findings indicate that interferon-beta (IFN-beta) plays a key role in the stimulatory cascade triggered by dsDNA. Both immune and non-immune cells respond to intracytoplasmic dsDNA by up-regulating IFN-beta) expression, a process that reduces host susceptibility to infection. The immune activation induced by dsDNA is independent of MyD88, TRIF and DNA-PKcs, indicating that a Toll-like receptor-independent mechanism underlies the cellular activation mediated by intracytoplasmic dsDNA.
authors.affiliation: Section of Retroviral Immunology, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, MD 20892, USA. shirota@cber.fda.gov
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Shirota
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takakuwa
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology; D033942:Adaptor Proteins, Vesicular Transport / Q000276:immunology; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000276:immunology*; D051747:DNA-Activated Protein Kinase / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005347:Fibroblasts / Q000821:virology; D006561:Herpes Simplex / Q000517:prevention & control; D018258:Herpesvirus 2, Human; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D053594:Myeloid Differentiation Factor 88; D009687:Nuclear Proteins / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection; D015854:Up-Regulation / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D016207:Cytokines; D004247:DNA; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D016899:Interferon-beta; D053594:Myeloid Differentiation Factor 88; D009687:Nuclear Proteins; D012333:RNA, Messenger; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; C476286:Ticam1 protein, mouse; C497264:Prkdc protein, mouse