Absent in melanoma 2 inflammasome (AIM2 inflammasome)

DNA sensor-dependent inflammasomes are innate immune complexes that form in response to cytosolic or nuclear DNA, typically during infection, cell damage, or stress. The best-characterized example is the AIM2 inflammasome, which is activated by double-stranded DNA (dsDNA) of at least 70–200 base pairs in length. AIM2 contains a HIN200 domain that binds DNA in a sequence-independent manner, and a pyrin domain that interacts with the adaptor ASC, which in turn recruits caspase-1, leading to maturation of inflammatory cytokines (IL-1β, IL-18) and induction of pyroptosis. IFI16 is another DNA sensor with weaker DNA affinity, but can assemble similar complexes and is particularly important for nuclear DNA sensing. NLRP3 may respond to DNA derivatives under specific conditions. These inflammasomes play essential roles in host defense, inflammatory and autoimmune diseases, cancer, and regulation of homeostasis. However, activation by self-DNA can promote pathological inflammation and autoimmunity. There are currently no approved drugs that directly target AIM2/IFI16 inflammasomes, though targeting the pathway is an area of therapeutic research.

Other names

AIM2 inflammasomeIFI16 inflammasomeNLRP3 inflammasomecytosolic DNA sensor inflammasomeDNA-induced inflammasome

Inhibition of inflammasome assembly, inhibition of caspase-1 activation, inhibition of IL-1β and IL-18 secretion, blockade of pyroptosis, and modulation of pattern recognition receptor signaling.