Intracellular DNA sensors in immunity.
Mammalian innate immunity possesses a distinct system to recognize aberrant DNA inside the cell. One class of DNA sensors is the Toll-like receptor 9, which is expressed in the specialized immune cells, binds to single-stranded DNA in the endosome to transmit cellular signaling through myeloid differentiation primary response protein 88 (MyD88). Another class of DNA sensors exists in the cytoplasm of most type of cells in the tissue, detecting double-stranded DNA to signal through TANK-binding kinase-1 (TBK1)-mediated type-I interferon production and apoptosis-associated speck-like protein containing a CARD (ASC)-mediated IL-1beta secretion. Since DNA sensors have potential to recognize aberrant DNA of both self and nonself origin, their physiological roles in microbial infection, tissue damage, autoimmune diseases, and DNA-based therapeutic applications are being intensively investigated.
Takeshita
Fumihiko
F
Department of Molecular Biodefense Research, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawaku, Yokohama, Japan. takesita@yokohama-cu.ac.jp
Ishii
Ken J
KJ
D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity; D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism; D004247:DNA / Q000276:immunology* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D051217:Toll-Like Receptor 9 / Q000276:immunology* / Q000378:metabolism; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000276:immunology / Q000378:metabolism
D053468:CARD Signaling Adaptor Proteins; D004268:DNA-Binding Proteins; D007370:Interferon Type I; D053594:Myeloid Differentiation Factor 88; D051217:Toll-Like Receptor 9; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D004247:DNA; D017346:Protein Serine-Threonine Kinases