Cited by 1,331Inflammasome and immune disordersImmune Response and Inflammationinterferon and immune responses

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The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses

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Rathinam, Vijay A K, Jiang, Zhaozhao, Waggoner, Stephen N, Sharma, Shruti, Cole, Leah E, Waggoner, Lisa, Vanaja, Sivapriya Kailasan, Monks, Brian G, Ganesan, Sandhya, Latz, Eicke, Hornung, Veit, Vogel, Stefanie N, Szomolanyi-Tsuda, Eva, Fitzgerald, Katherine A·2010·Nature Immunology

DOI 10.1038/ni.1864PMC PMC2887480

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Abstract

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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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: Rathinam, Vijay A K
Jiang, Zhaozhao
Waggoner, Stephen N
Sharma, Shruti
Waggoner, Lisa
Vanaja, Sivapriya Kailasan
Monks, Brian G
Ganesan, Sandhya
Latz, Eicke
Hornung, Veit
Vogel, Stefanie N
Fitzgerald, Katherine A
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2010-03-28
Volume: 11
Issue: 5
Pages: 395-402
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni.1864
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: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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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The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses

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