Contribution of interferon‐β to the immune activation induced by double‐stranded DNA

• Published in: Immunology Vol. 118; no. 3; pp. 302 - 310
• Main Authors: Shirota, Hidekazu, Ishii, Ken J., Takakuwa, Hiroki, Klinman, Dennis M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2006; Blackwell Science Inc
• Subjects: Adaptor Proteins, Signal Transducing - immunology; Adaptor Proteins, Vesicular Transport - immunology; Animals; Cytokines - biosynthesis; Cytokines - genetics; DNA; DNA - immunology; DNA-Activated Protein Kinase - immunology; DNA-Binding Proteins - immunology; Dose-Response Relationship, Immunologic; Female; Fibroblasts - virology; Herpes Simplex - prevention & control; Herpesvirus 2, Human; host protection; Interferon-beta - biosynthesis; Interferon-beta - immunology; Macrophages, Peritoneal - immunology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, SCID; Myeloid Differentiation Factor 88; Nuclear Proteins - immunology; Original; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; Toll‐like receptor; Transfection; type 1 IFNs; Up-Regulation - immunology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2006.02367.x

Summary 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‐β (IFN‐β) 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‐β) 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.