AIMing 2 Detect Foreign DNA

Arthur M. Krieg^*

Pfizer Research Technology Center, 620 Memorial Drive, Cambridge, MA 02139, USA.
^* E-mail, arthur.krieg{at}pfizer.com

Abstract: 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 1β (IL-1β). 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-1β. 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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