NLRP3 Inflammasome Pathway

The NLRP3 inflammasome pathway is an innate-immune signaling pathway that responds to infection and cell stress by assembling a multiprotein complex. This complex activates caspase-1, which processes the cytokines IL-1 beta and IL-18 into their active forms and triggers an inflammatory, often pyroptotic, response.

NLRP3 inflammasome activation requires two signals. The first is a priming signal, often through NF-kB, that boosts expression of NLRP3 and pro-IL-1 beta. The second is an activation signal from stimuli such as ATP, pore-forming toxins, or crystals that triggers assembly of the inflammasome complex.

The NLRP3 inflammasome is built from three core components: the NLRP3 sensor protein, the adaptor protein ASC, and pro-caspase-1. NLRP3 recruits ASC, which in turn recruits and activates caspase-1, forming the assembled complex that drives the inflammatory response.

Active caspase-1 cleaves the precursors pro-IL-1 beta and pro-IL-18 into mature IL-1 beta and IL-18, which are then secreted to amplify inflammation. Caspase-1 also cleaves gasdermin D, releasing a fragment that forms membrane pores and can drive an inflammatory cell death called pyroptosis.

Pyroptosis is an inflammatory form of programmed cell death triggered downstream of the NLRP3 inflammasome. After caspase-1 cleaves gasdermin D, the gasdermin D fragments form pores in the cell membrane, causing the cell to swell, rupture, and release inflammatory contents including mature IL-1 beta.

You can generate an NLRP3 inflammasome pathway diagram on SciFig: describe the priming and activation steps you need and the generator produces a labeled figure showing NLRP3, ASC, and caspase-1 assembly and IL-1 beta release. You then relabel the components and export it for a paper or talk.