Biochemical characterization of nucleic acid sensors in dendritic cellsGCOE Program Seminar(Global Education Seminar)

The innate immune system detects viral infection predominantly by sensing viral nuclei acids to produce type 1 interferon and proinflammatory cytokines. During the past decade, major efforts using genomic and genetic approaches have identified two major classes of innate immune receptors for sensing microbial nucleic acids: Toll-like receptors (TLR: TLR3, 7, 8, 9) and retinoic acid-inducible gene I-like helicases (RLH: RIG-I, LGP2, MDA-5). However, the genomic and genetic approaches have left a major gap in our understanding on how these receptors bind nucleic acids and whether additional receptors or coreceptors exist. We decided to open this “Black Box” by taking a biochemical approach to directly isolate and characterize microbial nucleic acid-binding proteins in innate immune cell types. Using this biochemical approach, we have identified many members of the DExD/H-box helicase family as novel cytosolic DNA and RNA sensors. In this presentation, DDX1, DDX21 and DHX36 as novel TRIF-dependent dsRNA sensors and DDX41 as novel STING-dependent cytosolic dsDNA sensor will be discussed. In addition, a novel helicase that sense dsRNA and activate NLRP3 inflammasome will be presented.