The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells

Nat Immunol. 2011 Sep 4;12(10):959-65. doi: 10.1038/ni.2091.

Abstract

The recognition of pathogenic DNA is important to the initiation of antiviral responses. Here we report the identification of DDX41, a member of the DEXDc family of helicases, as an intracellular DNA sensor in myeloid dendritic cells (mDCs). Knockdown of DDX41 expression by short hairpin RNA blocked the ability of mDCs to mount type I interferon and cytokine responses to DNA and DNA viruses. Overexpression of both DDX41 and the membrane-associated adaptor STING together had a synergistic effect in promoting Ifnb promoter activity. DDX41 bound both DNA and STING and localized together with STING in the cytosol. Knockdown of DDX41 expression blocked activation of the mitogen-activated protein kinase TBK1 and the transcription factors NF-κB and IRF3 by B-form DNA. Our results suggest that DDX41 is an additional DNA sensor that depends on STING to sense pathogenic DNA.

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Cells, Cultured
  • DEAD-box RNA Helicases / physiology*
  • DNA / metabolism*
  • DNA Helicases / physiology*
  • Dendritic Cells / physiology*
  • Humans
  • Interferons / biosynthesis
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / virology
  • Protein Structure, Tertiary
  • Signal Transduction

Substances

  • Membrane Proteins
  • STING protein, human
  • Sting1 protein, mouse
  • DNA
  • Interferons
  • DDX41 protein, human
  • DNA Helicases
  • DDX41 protein, mouse
  • DEAD-box RNA Helicases