Inflammasomes are large cytoplasmic complexes that sense pathogen-associated and danger signals, but the molecular mechanisms of inflammasome activation are unclear. In Nature, Shao and colleagues show that NAIP proteins function as receptors for bacterial flagellin and type III secretion system (TTSS) proteins to activate the NLRC4 (IPAF) inflammasome. NAIP5 directly and specifically interacts with flagellin, and this promotes NAIP5-NLRC4 association. In an analogous way, NAIP2 serves as a receptor for TTSS rod proteins such as Salmonella PrgJ and Burkholderia BsaK. Human NAIP functions analogously to mouse NAIP2 and NAIP5 in recognizing the TTSS needle subunit (cprI) of Chromobacterium violaceum and triggering NLRC4 inflammasome activation. The inflammasome-activating activities of flagellin and TTSS rod and needle proteins lie in their C-terminal leucine-rich regions, which share structural features.

Nature (15 September 2011) doi:10.1038/nature10510