Critical role of AIM2 in Mycobacterium tuberculosis infection.
Absent in melanoma 2 (AIM2) is a sensor of cytosolic DNA that is responsible for activation of the inflammasome and host immune responses to DNA viruses and intracellular bacteria. However, the role of AIM2 in host defenses against Mycobacterium tuberculosis is unknown. Here, we show that AIM2-deficient mice were highly susceptible to intratracheal infection with M. tuberculosis and that this was associated with defective IL-1β and IL-18 production together with impaired T (h) 1 responses. Macrophages from AIM2-deficient mice infected with M. tuberculosis showed severely impaired secretion of IL-1β and IL-18 as well as activation of the inflammasome, determined by caspase-1 cleavage. Genomic DNA extracted from M. tuberculosis (Mtb DNA) induced caspase-1 activation and IL-1β/IL-18 secretion in an AIM2-dependent manner. Mtb DNA, which was present in the cytosol, co-localized with AIM2. Taken together, these findings demonstrate that AIM2 plays an important role in M. tuberculosis infection through the recognition of Mtb DNA.
Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University,  Suita, Osaka 565-0871, Japan.
Hiroyuki
H
Saiga
Shoko
S
Kitada
Yosuke
Y
Shimada
Naganori
N
Kamiyama
Megumi
M
Okuyama
Masahiko
M
Makino
Masahiro
M
Yamamoto
Kiyoshi
K
Takeda
D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D005260:Female; D058847:Inflammasomes / Q000276:immunology; D007375:Interleukin-1 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity*; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
C540422:Aim2 protein, mouse; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D007375:Interleukin-1; D020382:Interleukin-18; D009687:Nuclear Proteins; D020170:Caspase 1