The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses
Authors
Rathinam, Vijay A.K.Jiang, Zhaozhao
Waggoner, Stephen N.
Sharma, Shrutie
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.
UMass Chan Affiliations
Department of PathologyDepartment of Medicine, Division of Infectious Diseases and Immunology
Department of Molecular Genetics and Microbiology
Document Type
Journal ArticlePublication Date
2010-03-31Keywords
AnimalsCaspase 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
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
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.Source
Nat Immunol. 2010 May;11(5):395-402. Epub 2010 Mar 28. Link to article on publisher's siteDOI
10.1038/ni.1864Permanent Link to this Item
http://hdl.handle.net/20.500.14038/35215PubMed ID
20351692Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/ni.1864