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Publication : Critical role of AIM2 in Mycobacterium tuberculosis infection.

First Author  Saiga H Year  2012
Journal  Int Immunol Volume  24
Issue  10 Pages  637-44
PubMed ID  22695634 Mgi Jnum  J:188013
Mgi Id  MGI:5438896 Doi  10.1093/intimm/dxs062
Citation  Saiga H, et al. (2012) Critical role of AIM2 in Mycobacterium tuberculosis infection. Int Immunol 24(10):637-44
abstractText  Abstract 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-1+/- 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-1+/- 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-1+/-/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.
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