Cellular signaling, molecular activation, and regulation of the AIM2 inflammasome

Absent in melanoma 2 (AIM2) is a cytosolic receptor that recognizes double-stranded DNA (dsDNA) and triggers the activation of the inflammasome cascade. Activation of the inflammasome then leads to the maturation and release of inflammatory cytokines of the interleukin 1 (IL-1) family, such as IL-1β and IL-18, and to inflammatory cell death due to pyroptosis. Due to the highly conserved nature of its ligand, AIM2 is a key mechanism for immune recognition of multiple pathogens. In addition, AIM2 is also capable of binding dsDNA from the host's own damage cells, thereby sensing tissue damage. Hence, AIM2 may function either as a pattern recognition receptor that senses pathogen-associated molecular patterns or as an alarmin receptor that senses damage-associated molecular patterns In this chapter, we discuss the current knowledge of AIM2 inflammasome signaling, activation, and regulation.