Absent in
melanoma 2 (AIM2) is a cytoplasmic sensor that upon recognizing
double-stranded DNA assembles with apoptosis-associated speck-like
protein containing a CARD (ASC) and
procaspase-1 to form the multi-
protein complex AIM2
inflammasome.
Double-stranded DNA from bacterial, viral, or host cellular origins triggers AIM2
inflammasome assembly and activation, ultimately resulting in secretion of proinflammatory
cytokines and pyroptotic cell death in order to eliminate microbial
infection. Many pathogens therefore evade or suppress AIM2
inflammasome to establish
infection. On the other hand, AIM2 activation is tightly controlled by multiple cellular factors to prevent autoinflammation. Extensive structural studies have captured the molecular details of multiple steps in AIM2
inflammasome assembly. The structures collectively revealed a nucleated polymerization mechanism that not only pervades each step of AIM2
inflammasome assembly, but also underlies assembly of other
inflammasomes and complexes in immune signaling. In this article, we briefly review the identification of AIM2 as a cytoplasmic
DNA sensor, summarize the importance of AIM2
inflammasome in
infections and diseases, and discuss the molecular mechanisms of AIM2 assembly, activation, and regulation using recent cellular, biochemical, and structural results.