Cytosolic nucleic acid sensors and innate immune regulation.
During viral and bacterial infections, pathogen-derived cytosolic nucleic acids are recognized by the intracellular RNA sensors retinoic acid-inducible gene I and melanoma-differentiated gene 5 and intracellular DNA sensors, including cyclic-di-GMP-AMP synthase, absent in melanoma 2, interferon (IFN)-gamma inducible protein 16, polymerase III, and so on. Binding of intracellular nucleic acids to these sensors activates downstream signaling cascades, resulting in the production of type I IFNs and pro-inflammatory cytokines to induce appropriate systematic immune responses. While these sensors also recognize endogenous nucleic acids and activate immune responses, they can discriminate between self- and non-self-nucleic acids. However, dysfunction of these sensors or failure of regulatory mechanisms causes aberrant activation of immune response and autoimmune disorders. In this review, we focus on how intracellular immune sensors recognize exogenous nucleic acids and activate the innate immune system, and furthermore, how autoimmune diseases result from dysfunction of these sensors.
a Laboratory of Molecular Immunobiology , Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Takayama-cho , Ikoma , Nara , Japan.
Daisuke
D
Ori
a Laboratory of Molecular Immunobiology , Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Takayama-cho , Ikoma , Nara , Japan.
Motoya
M
Murase
a Laboratory of Molecular Immunobiology , Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Takayama-cho , Ikoma , Nara , Japan.
Taro
T
Kawai
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D003600:Cytosol / Q000378:metabolism; D000071457:DEAD Box Protein 58 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006790:Host-Parasite Interactions; D006801:Humans; D007113:Immunity, Innate; D000072640:Interferon-Induced Helicase, IFIH1 / Q000378:metabolism*; D009696:Nucleic Acids / Q000276:immunology*; D011971:Receptors, Immunologic; D051192:Receptors, Pattern Recognition / Q000378:metabolism; D017634:Self Tolerance; D015398:Signal Transduction
C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; D009696:Nucleic Acids; D011971:Receptors, Immunologic; D051192:Receptors, Pattern Recognition; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D000072640:Interferon-Induced Helicase, IFIH1; D000262:Adenylyl Cyclases
DNA sensors; Immunity; RNA sensors; innate immunity; intracellular nucleic acid