The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses
Department of Molecular Genetics and Microbiology; Department of Medicine, Division of Infectious Diseases and Immunology; Department of Pathology
Animals; Caspase 1; Cell Line; Cytokines; Cytoskeletal Proteins; DNA; DNA Virus Infections; DNA Viruses; Francisella tularensis; Humans; Immunity, Innate; Killer Cells,; Natural; Listeriosis; Lymphocyte Activation; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Multiprotein Complexes; Nuclear Proteins; Signal Transduction; Transcription Factors; Tularemia; Viral Load
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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Citation: Nat Immunol. 2010 May;11(5):395-402. Epub 2010 Mar 28. Link to article on publisher's site