title: STING recognition of cytoplasmic DNA instigates cellular defense.
abstract: How the cell recognizes cytosolic DNA including DNA-based microbes to trigger host-defense-related gene activation remains to be fully resolved. Here, we demonstrate that STING (stimulator of interferon genes), an endoplasmic reticulum translocon-associated transmembrane protein, acts to detect cytoplasmic DNA species. STING homodimers were able to complex with self- (apoptotic, necrotic) or pathogen-related ssDNA and dsDNA and were indispensible for HSV-1-mediated transcriptional activation of a wide array of innate immune and proinflammatory genes in addition to type I IFN. Our data indicate that STING instigates cytoplasmic DNA-mediated cellular defense gene transcription and facilitates adoptive responses that are required for protection of the host. In contrast, chronic STING activation may manifest inflammatory responses and possibly autoimmune disease triggered by self-DNA.
authors.affiliation: Department of Cell Biology and the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Abe
authors.forename: Ai
authors.initials: A
authors.lastname: Harashima
authors.forename: Tianli
authors.initials: T
authors.lastname: Xia
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Konno
authors.forename: Keiko
authors.initials: K
authors.lastname: Konno
authors.forename: Alejo
authors.initials: A
authors.lastname: Morales
authors.forename: Jeonghyun
authors.initials: J
authors.lastname: Ahn
authors.forename: Delia
authors.initials: D
authors.lastname: Gutman
authors.forename: Glen N
authors.initials: GN
authors.lastname: Barber
mesh_terms: D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D003593:Cytoplasm / Q000276:immunology / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000276:immunology / Q000378:metabolism*; D017930:Genes, Reporter; D057809:HEK293 Cells; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009336:Necrosis; D055503:Protein Multimerization; D034622:RNA Interference; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D000099197:STING Protein
chemical_list: D004277:DNA, Single-Stranded; D018836:Inflammation Mediators; D007370:Interferon Type I; D049409:Luciferases, Firefly; D008565:Membrane Proteins; D019098:Telomerase; C532857:STING1 protein, human; D000099197:STING Protein; C509186:TERT protein, human