The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses.
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.
Rathinam
Vijay A K
VA
Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA .
Jiang
Zhaozhao
Z
Waggoner
Stephen N
SN
Sharma
Shruti
S
Cole
Leah E
LE
Waggoner
Lisa
L
Vanaja
Sivapriya Kailasan
SK
Monks
Brian G
BG
Ganesan
Sandhya
S
Latz
Eicke
E
Hornung
Veit
V
Vogel
Stefanie N
SN
Szomolanyi-Tsuda
Eva
E
Fitzgerald
Katherine A
KA
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics; D004247:DNA / Q000276:immunology; D004266:DNA Virus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004267:DNA Viruses / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D004268:DNA-Binding Proteins; D005604:Francisella tularensis / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014406:Tularemia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load / Q000235:genetics / Q000276:immunology
C540422:Aim2 protein, mouse; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D016207:Cytokines; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C498534:Pycard protein, mouse; D014157:Transcription Factors; D004247:DNA; D020170:Caspase 1