The NLRP3 Inflammasome

We are investigating how the NLRP3 inflammasome is activated in response to diverse stimuli. NLRP3 is implicated in the pathophysiology of many autoinflammatory, autoimmune, metabolic and infectious diseases. NLRP3 is activated by a wide-range of molecules including crystals formed in gout and atherosclerosis, viruses and bacterial toxins, but the mechanisms by which NLRP3 senses and elicits a response to these chemically and structurally dissimilar stimuli remain elusive. We are investigating the role of mitochondrial and other subcellular structures in NLRP3 inflammasome activation and how this key organelle controls not only NLRP3 inflammasome activity but also other innate sensing pathways converging on the mitochondria. These questions follow from our previous work showing that mitochondrial recruitment of NLRP3, increased cytoplasmic calcium and decreased cyclic AMP are important early events in NLRP3 inflammasome activation.