Cited by 732Inflammasome and immune disordersImmune Response and InflammationBacillus and Francisella bacterial research

The AIM2 inflammasome is critical for innate immunity to Francisella tularensis

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Fernandes-Alnemri, Teresa, Yu, Je-Wook, Juliana, Christine, Solorzano, Leobaldo, Kang, Seokwon, Wu, Jianghong, Datta, Pinaki, McCormick, Margaret +5 more·2010·Nature Immunology

Abstract

Francisella tularensis, the causative agent of tularemia, infects host macrophages, which triggers production of the proinflammatory cytokines interleukin 1beta (IL-1beta) and IL-18. We elucidate here how host macrophages recognize F. tularensis and elicit this proinflammatory response. Using mice deficient in the DNA-sensing inflammasome component AIM2, we demonstrate here that AIM2 is required for sensing F. tularensis. AIM2-deficient mice were extremely susceptible to F. tularensis infection, with greater mortality and bacterial burden than that of wild-type mice. Caspase-1 activation, IL-1beta secretion and cell death were absent in Aim2(-/-) macrophages in response to F. tularensis infection or the presence of cytoplasmic DNA. Our study identifies AIM2 as a crucial sensor of F. tularensis infection and provides genetic proof of its critical role in host innate immunity to intracellular pathogens.

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  • 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 [51]

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Authors
Fernandes-Alnemri, T., Yu, J.-W., Juliana, C., Solorzano, L., Kang, S., Wu, J., Datta, P., McCormick, M., Huang, L., McDermott, E., Eisenlohr, L., Landel, C. P., & Alnemri, E. S.
Affiliations
Thomas Jefferson University (US)
Corresponding author
Alnemri, Emad S
Venue
Nature Immunology
Published
2010-03-28
Volume
11
Issue
5
Pages
385-393
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W2157305255
Cited by
732
References
45
Citations by year
2026: 26 · 2025: 19 · 2024: 34 · 2023: 22 · 2022: 25 · 2021: 35 · 2020: 30 · 2019: 39 · 2018: 42 · 2017: 60 · 2016: 53 · 2015: 57 · 2014: 58 · 2013: 73 · 2012: 51
FWCI
29.95
Type
journal article
Language
en
Open access
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Harvard University
  • National Institutes of Health
  • National Institute on Aging (AG14357, R01AG014357)
  • National Cancer Institute (T32 CA09678, T32CA009678)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-055398, R01AR055398)
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacillus and Francisella bacterial research
Keywords
AIM2 inflammasome, Francisella tularensis, tularemia, innate immunity, macrophages, cytosolic DNA sensing, caspase-1 activation, IL-1β, IL-18, intracellular bacterial infection, host defense
MeSH terms
Animals, Cells, Cultured, DNA-Binding Proteins, Francisella tularensis, Humans, Immunity, Innate, Interferon Type I, L-Lactate Dehydrogenase, Macrophages, Nuclear Proteins, Tularemia, Mice, Knockout, Calcium Signaling, Caspase 1, Multiprotein Complexes, Interferon Regulatory Factor-3, Mice, Interleukin-1beta, Protein Multimerization

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