[5][6] AIM2 is a cytoplasmic sensor found in hematopoietic cells that recognizes the presence of double-stranded DNA (dsDNA) of microbial or host cellular origin.

[8] Activated AIM2 recruits apoptosis-associated speck-like protein containing a CARD (ASC), resulting in caspase-1 binding, and forming of AIM2 inflammasome.

[11] AIM2 is a component of the innate immune system that functions as a cytoplasmic dsDNA sensor playing a role in antiviral and antibacterial defenses, as well as in autoimmune diseases involving self DNA.

[12] The interaction is mainly electrostatic, where positively charged amino acid residues are coordinating with phosphates and sugar moieties on DNA backbone.

Binding of dsDNA displaces PYD domain, which then engages the downstream inflammasome adaptor protein ASC through homotypic PYD-PYD interactions.

CARD domain of ASC recruits procaspase-1 (CARD-CARD interaction) to the complex creating the basic structural elements of the AIM2 inflammasome.

[14][15] PANoptosomes are multi-protein complexes assembled by germline-encoded pattern-recognition receptor(s) (PRRs) (innate immune sensor(s)) in response to pathogens, including bacterial, viral, and fungal infections, as well as pathogen-associated molecular patterns, damage-associated molecular patterns, cytokines, and homeostatic changes during infections, inflammatory conditions, and cancer.

[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] To form the PANoptosome, the AIM2 inflammasome further interacts with caspase-8, FADD, RIPK3, and RIPK1 in response to specific pathogens, including Francisella novicida and herpes simplex virus 1 (HSV1), to drive PANoptosis.

AIM2 has been shown to recognize a number of pathogenic bacteria – Francisella tularensis, Listeria monocytogenes, Streptococcus pneumoniae, Mycobacterium species, Porphyromonas gingivalis, Staphylococcus aureus, Brucella abortus, and Chlamydia muridarum.

[9] AIM2 inflammasome plays a crucial role in the defense against viral infection as genetic material from DNA viruses that enter the cytoplasm can be recognized.

[7] In systemic lupus erythematosus, lysosome dysfunction allows DNA to gain access to the cytosol and activate AIM2 resulting in increased type 1 interferon production.