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Sci Signal. 2009 Jun 30;2(77):pe39. doi: 10.1126/scisignal.277pe39.

AIMing 2 detect foreign DNA.

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Pfizer Research Technology Center, 620 Memorial Drive, Cambridge, MA 02139, USA.


Foreign genomic DNA can be detected by immune cells in the cytoplasm, triggering reactions such as cell death and secretion of proinflammatory cytokines, including interleukin 1beta (IL-1beta). Several studies have now elucidated the mechanism for this response. The HIN-200 (hematopoietic interferon-inducible nuclear proteins with a 200-amino acid repeat) family member AIM2 (absent in melanoma 2) binds and oligomerizes on cytoplasmic DNA through a HIN domain. The oligomerized AIM2 recruits the adaptor ASC (apoptosis-associated specklike protein containing a CARD) through homotypic pyrin domain interactions and binds caspase-1, forming an inflammasome that generates IL-1beta. Together with previous studies, this work demonstrates that immune detection of foreign nucleic acids occurs through several distinct signaling pathways, leading to diverse immune outcomes.

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