Recognition of cytosolic DNA activates an IRF3-dependent innate immune response

Immunity. 2006 Jan;24(1):93-103. doi: 10.1016/j.immuni.2005.12.003.


Nucleic acid recognition upon viral infection triggers type I interferon production. Viral RNA is detected by both endosomal, TLR-dependent and cytosolic, RIG-I/MDA5-dependent pathways. TLR9 is the only known sensor of foreign DNA; it is unknown whether innate immune recognition of DNA exists in the cytosol. Here we present evidence that cytosolic DNA activates a potent type I interferon response to the invasive bacterium Listeria monocytogenes. The noninvasive Legionella pneumophila triggers an identical response through its type IV secretion system. Activation of type I interferons by cytosolic DNA is TLR independent and requires IRF3 but occurs without detectable activation of NF-kappaB and MAP kinases. Microarray analyses reveal a unique but overlapping gene-expression program activated by cytosolic DNA compared to TLR9- and RIG-I/MDA5-dependent responses. These findings define an innate immune response to DNA linked to type I interferon production.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cytosol / chemistry
  • DNA, Bacterial / analysis
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / immunology*
  • Gene Expression
  • Immunity, Innate* / genetics
  • Interferon Regulatory Factor-3 / genetics
  • Interferon Regulatory Factor-3 / metabolism*
  • Interferon-beta / genetics
  • Interferon-beta / metabolism*
  • Legionella pneumophila / genetics
  • Legionella pneumophila / immunology*
  • Ligands
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / immunology*
  • Mice
  • Mice, Mutant Strains
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • NF-kappa B / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Sugar Phosphates / analysis
  • Sugar Phosphates / immunology


  • DNA, Bacterial
  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • Ligands
  • NF-kappa B
  • Sugar Phosphates
  • Interferon-beta
  • Mitogen-Activated Protein Kinase Kinases