The Mechanism of NLRP3 Inflammasome Activation and Its Roles in Chronic Rhinosinusitis

NLRP3 (NLR family pyrin domain containing 3) is one of the crucial receptors in pathogen recognition receptor (PRR) families which can recognize the pathogen-associated molecular patterns (PAMPs) and the damage-associated molecular patterns (DAMPs), thus triggering innate immune response. After NLRP3 activation, it recruits the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) and the effector protein caspase-1 (CASP-1) to form a multiprotein complex, which is named NLRP3 inflammasome, enables the cleavage of caspase-1. Furthermore, the active c-caspase-1 proteolytically cleaves GSDMD into N-GSDMD, which forms pores on the membrane, thus inducing the leakage of pro-inflammatory cytokines, including IL-1β and IL-18, which leads to lytic cell death, defined as pyroptosis. Recent studies suggest that the abnormal activation of NLRP3 inflammasome in human nasal epithelial cells, mucosal T lymphocytes, and mucosal macrophages is associated with the pathogenesis of chronic rhinosinusitis (CRS). However, the underlying mechanism is still unclear. To provide further perspective on how the NLRP3 inflammasome is activated in CRS, this review focuses on the structure-derived assembly and activation of the NLRP3 inflammasome, and its roles and the potential activation mechanism in CRS. We also discuss major cellular stress signals that trigger the NLRP3 inflammasome.