Cited by 1,091Inflammasome and immune disordersinterferon and immune responsesImmune Response and Inflammation

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

Bürckstümmer, Tilmann, Baumann, Christoph, Blüml, Stephan, Dixit, Evelyn, Dürnberger, Gerhard, Jahn, Hannah, Planyavsky, Melanie, Bilban, Martin +3 more·2009·Nature Immunology

Abstract

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.

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Crossref · 10.1038/ni.1702

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  • The AIM2 inflammasome has been shown to recognize cytoplasmic double-stranded DNA (dsDNA) that is not necessarily microbial in origin, resulting in caspase 1 activation and IL-1β secretion.

    “The AIM2 inflammasome has been recently shown to recognize cytoplasmic double-stranded DNA (dsDNA) that is not necessarily microbial in origin, resulting in caspase 1 activation and IL-1β secretion48–50.”

    From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [48]

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Authors
Bürckstümmer, T., Baumann, C., Blüml, S., Dixit, E., Dürnberger, G., Jahn, H., Planyavsky, M., Bilban, M., Colinge, J., Bennett, K. L., & Superti-Furga, G.
Affiliations
  • Austrian Academy of Sciences (AT)
  • Medical University of Vienna (AT)
Venue
Nature Immunology
Published
2009-01-21
Volume
10
Issue
3
Pages
266-272
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W2072118838
Cited by
1,091
References
27
Citations by year
2026: 28 · 2025: 33 · 2024: 51 · 2023: 48 · 2022: 47 · 2021: 44 · 2020: 55 · 2019: 55 · 2018: 56 · 2017: 61 · 2016: 55 · 2015: 64 · 2014: 67 · 2013: 85 · 2012: 78
FWCI
45.85
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
AIM2, inflammasome, innate immunity, ASC, caspase-1, THP-1 cells
MeSH terms
Animals, Cytosol, DNA, DNA-Binding Proteins, Humans, Immunity, Innate, Nuclear Proteins, Interferon-beta, Caspase 1, Gene Expression Profiling, Genomics, Proteomics, NIH 3T3 Cells, Adaptor Proteins, Signal Transducing, Mice, Interleukin-1beta

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