Figure 1. The AIM2-containing inflammasome recognizes self-DNA.

The PYHIN protein AIM2 is activated in response to DNA in the cytoplasm and interacts with ASC and caspase-1 to form an inflammasome. Inflammasome activation leads to maturation of the proinflammatory cytokines IL-1β and IL-18 and to pyroptotic cell death. Overall, AIM2 activation contributes to sterile inflammatory processes when self-DNA fragments from damaged host cells escape endosomes due to mutations in DNases or endosomal maturation and self-DNA enters the cytoplasm. In order for this inflammatory process to progress, a priming signal is generally required for production of pro-IL-1β. In “sterile inflammation” mediated by AIM2, this priming signal has not been directly determined but may depend on endogenous DNA, other endogenous ligands or on pathogen associated molecular patterns derived from the host microbiota.