AIMing 2 Detect Foreign DNA

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 1 beta (IL-1 beta). 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-1 beta. 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.