Critical role for the AIM2 inflammasome during acute CNS bacterial infection

The AIM2 inflammasome is protective during acute CNS bacterial infection. A disconnect in phenotypes between the inflammasome sensor Nod-like receptor protein 3 (NLRP3) and its adaptor ASC (apoptosis-associated speck-like protein containing a caspase-1 recruitment domain) during acute CNS Staphylococcus aureus (S. aureus) infection led to the discovery of absent in melanoma 2 (AIM2) as a critical inflammasome sensor. The AIM2 inflammasome is potentially triggered by dsDNA in cells harboring intracellular S. aureus, leading to ASC and caspase 1 recruitment, resulting in pro-IL-1 processing and cytokine secretion. This cascade, in turn, is protective to the host during acute infection. The NLRP3 inflammasome is also activated in response to S. aureus challenge by -hemolysin (hla); however, it is not critical for host survival. ASC also regulates the production of other inflammatory mediators, presumably via indirect effects mediated by IL-1 action.