An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome

Nat Immunol. 2009 Mar;10(3):266-72. doi: 10.1038/ni.1702. Epub 2009 Jan 21.


Cytoplasmic DNA triggers activation of the innate immune system. Although 'downstream' signaling components have been characterized, the DNA-sensing components remain elusive. Here we present a systematic proteomics screen for proteins that associate with DNA, 'crossed' to a screen for transcripts induced by interferon-beta, which identified AIM2 as a candidate cytoplasmic DNA sensor. AIM2 showed specificity for double-stranded DNA. It also recruited the inflammasome adaptor ASC and localized to ASC 'speckles'. A decrease in AIM2 expression produced by RNA-mediated interference impaired DNA-induced maturation of interleukin 1beta in THP-1 human monocytic cells, which indicated that endogenous AIM2 is required for DNA recognition. Reconstitution of unresponsive HEK293 cells with AIM2, ASC, caspase-1 and interleukin 1beta showed that AIM2 was sufficient for inflammasome activation. Our data suggest that AIM2 is a cytoplasmic DNA sensor for the inflammasome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Caspase 1 / immunology
  • Caspase 1 / metabolism
  • Cytosol / metabolism
  • DNA / immunology
  • DNA / metabolism*
  • DNA-Binding Proteins
  • Gene Expression Profiling
  • Genomics / methods
  • Humans
  • Immunity, Innate
  • Interferon-beta / immunology
  • Interferon-beta / metabolism
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism
  • Mice
  • NIH 3T3 Cells
  • Nuclear Proteins / immunology
  • Nuclear Proteins / metabolism*
  • Proteomics / methods


  • AIM2 protein, human
  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • Interleukin-1beta
  • Nuclear Proteins
  • Interferon-beta
  • DNA
  • Caspase 1

Associated data

  • GEO/GSE14413