What activates NLRP3 inflammasome?

Studies show that the NLRP3 inflammasome may be activated by diverse inflammatory stimuli including mitochondrial dysfunction, lysosomal damage, abnormal ionic flux, and the production of reactive oxygen species (ROS), all of which can be caused by a viral infection.

NLRP3 inflammasome activation and assembly may be triggered by K+ efflux, which is induced by extracellular adenosine triphosphate (ATP). In this case, ATP acts as an NLRP3 agonist.

NLRP3 inflammasome may also be activated by all known Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs). The PAMPS and DAMPS trigger the generation of reactive oxygen species (ROS), which then induces NLRP3 activation and assembly.

Certain environmental irritants such as asbestos, alum, silica, and amyloid-β, as well as mitochondrial damage or dysfunction caused by mitochondrial Ca2+ overload are other factors that may also trigger the activation and assembly of NLRP3 inflammasome.

Activation of the NLRP3 inflammasome appears to occur in two steps. The first step involves a priming or initiating signal in which many PAMPs or DAMPs are recognized by Toll-like receptors (TLRs). The second step involves the oligomerization of NLRP3 and subsequent assembly of NLRP3, procaspase-1, and ASC into a complex.