Figure 1.

NLRP3 inflammasome activation by pneumococci. Pneumococci secrete two major virulence determinants: pneumolysin (PLY) and hydrogen peroxide (H₂O₂). In neutrophils (PMN), PLY-mediated NLRP3 activation is a result of K⁺ efflux. K⁺ efflux activates NLRP3 inflammasome resulting in caspase-1 activation and subsequent cleavage of pro-IL-1β into mature form. In macrophages, PLY-mediated NLRP3 inflammasome activation is among others dependent on ATP. The released IL-1β stimulates epithelial cells. As a result, they release chemoattractants, including CXCL1 and CXCL2. Both chemokines are involved in processes resulting in neutrophil influx. Furthermore, IL-1β is involved in T helper type 17 cells differentiation and subsequent IL-17A release. In contrast to PLY, H₂O₂ suppresses NLRP3 inflammasome in macrophages (MΦ) resulting in pro-IL-1β accumulation in these cells (APC, antigen presenting cell).