Cytosolic nucleic acid sensors and innate immune regulation

• Published in: International reviews of immunology Vol. 36; no. 2; pp. 74 - 88
• Main Authors: Ori, Daisuke, Murase, Motoya, Kawai, Taro
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04-03-2017
• Subjects: Adenylyl Cyclases - metabolism; Animals; Autoimmune Diseases - immunology; Cytosol - metabolism; DEAD Box Protein 58 - metabolism; DNA sensors; DNA-Binding Proteins - metabolism; Host-Parasite Interactions; Humans; Immunity; Immunity, Innate; innate immunity; Interferon-Induced Helicase, IFIH1 - metabolism; intracellular nucleic acid; Nucleic Acids - immunology; Receptors, Immunologic; Receptors, Pattern Recognition - metabolism; RNA sensors; Self Tolerance; Signal Transduction; innate immunity; Immunity; intracellular nucleic acid; DNA sensors; RNA sensors
• ISSN: 0883-0185; 1563-5244
• DOI: 10.1080/08830185.2017.1298749

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.