The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses
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Inflammasomes regulate the activity of caspase-1 and the maturation of interleukin 1beta (IL-1beta) and IL-18. AIM2 has been shown to bind DNA and engage the caspase-1-activating adaptor protein ASC to form a caspase-1-activating inflammasome. Using Aim2-deficient mice, we identify a central role for AIM2 in regulating caspase-1-dependent maturation of IL-1beta and IL-18, as well as pyroptosis, in response to synthetic double-stranded DNA. AIM2 was essential for inflammasome activation in response to Francisella tularensis, vaccinia virus and mouse cytomegalovirus and had a partial role in the sensing of Listeria monocytogenes. Moreover, production of IL-18 and natural killer cell-dependent production of interferon-gamma, events critical in the early control of virus replication, were dependent on AIM2 during mouse cytomegalovirus infection in vivo. Collectively, our observations demonstrate the importance of AIM2 in the sensing of both bacterial and viral pathogens and in triggering innate immunity.
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Interleukin-1β secretion depends on the inflammasome, a caspase-1-containing complex.
“Finally, the authors found no secretion of the proinflammatory cytokine interleukin-1β, a process known to depend on the inflammasome—a caspase-1-containing complex (122).”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [122]
AIM2 has a demonstrated role in immune responses directed against both bacteria and DNA viruses.
“AIM2 has a demonstrated role in immune responses directed against both bacteria51 and DNA viruses52, but it will be important to determine whether there is a physiological role for AIM2 in sterile inflammation, especially in autoimmune diseases such as systemic lupus erythematosus, which is associated with elevated circulating levels of dsDNA.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [52]
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- Authors
- Rathinam, V. A. K., Jiang, Z., Waggoner, S. N., Sharma, S., Cole, L. E., Waggoner, L., Vanaja, S. K., Monks, B. G., Ganesan, S., Latz, E., Hornung, V., Vogel, S. N., Szomolanyi-Tsuda, E., & Fitzgerald, K. A.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- University of Maryland, Baltimore (US)
- University of Bonn (DE)
- Corresponding author
- Fitzgerald, Katherine A
- ORCID
- Venue
- Nature Immunology
- Published
- 2010-03-28
- Volume
- 11
- Issue
- 5
- Pages
- 395-402
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC2887480
- OpenAlex
- W2104195963
- Cited by
- 1,331
- References
- 53
- Citations by year
- 2026: 42 · 2025: 52 · 2024: 74 · 2023: 64 · 2022: 66 · 2021: 68 · 2020: 80 · 2019: 89 · 2018: 70 · 2017: 89 · 2016: 95 · 2015: 90 · 2014: 103 · 2013: 108 · 2012: 72
- FWCI
- 44.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship@UMassChan (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Cancer Institute (CA 66644, R01CA066644, CA034461, R01CA034461)
- National Institute of Allergy and Infectious Diseases (AI-07349, U54 AI157168, AI083713, R01AI083713, T32AI007349)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- AIM2 inflammasome, caspase-1, IL-1β maturation, pyroptosis, innate immunity, cytosolic bacteria, DNA viruses, Francisella tularensis, vaccinia virus, murine cytomegalovirus, Listeria monocytogenes, interferon-gamma, natural killer cells, double-stranded DNA sensing
- MeSH terms
- Animals, Cell Line, Cytoskeletal Proteins, DNA, DNA Virus Infections, DNA Viruses, DNA-Binding Proteins, Francisella tularensis, Humans, Immunity, Innate, Killer Cells, Natural, Listeriosis, Lymphocyte Activation, Macrophages, Mice, Inbred C57BL, Nuclear Proteins, Transcription Factors, Tularemia, Signal Transduction, Cytokines, Mice, Knockout, Viral Load, Caspase 1, Multiprotein Complexes, Apoptosis Regulatory Proteins, Mice, CARD Signaling Adaptor Proteins
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