FIG. 1.

Four major types of inflammasomes and their known stimulators. Nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP1), proposed to be activated by bacterial cell wall component muramyl dipeptide (MDP) and Bacillus anthracis lethal toxin, can directly cause caspase-5 processing, but the presence of adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) results in more robust activation. NLRC4 activation is mostly associated with gram-negative bacteria components and can also directly process caspase-1 through its caspase recruitment domain (CARD). Double-stranded DNA (dsDNA) binds preferentially to the HIN200 domain of AIM2 (absent in melanoma 2), and requires ASC for caspase-1 processing. NLRP3 also requires ASC and caspase-1, is activated in response to both exogenous and endogenous danger signals, and is mostly recognized for its role in sterile inflammation. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars