Figure 1.
Stimuli and composition of distinct inflammasomes.
The NLR proteins NALP1b, Cryopyrin/NALP3, and IPAF and the HIN-200 protein AIM2 assemble a caspase-1 activating inflammasome complex in response to specific microbial or bacterial factors. The murine NALP1b inflammasome recognizes the cytosolic presence of anthrax LT. The Cryopyrin/NALP3 inflammasome recognizes multiple PAMPs in combination with ATP or nigericin, as well as crystalline substances including MSU, silica, and asbestos particles. The IPAF inflammasome senses Salmonella and Legionella flagellin and a yet unidentified Shigella flexneri compound, which all access the cytosol through a type III or IV secretion system. Cytosolic PAMPs may trigger assembly of a particular inflammasome complex by causing modifications in unknown host factors (X, Y, Z) that are monitored by specific NLR proteins. In contrast, AIM2 directly binds dsDNA in the cytosol to induce caspase-1 activation. The CARD/pyrin-containing adaptor protein ASC is essential for all these inflammasome complexes, although its role in the NALP1b inflammasome remains to be formally established. Once activated, caspase-1 processes the IL-1β and IL-18 precursors into the mature cytokines, which are secreted through an unknown mechanism.