Figure 2.

Mechanism of Activation for the Non-Canonical and Alternative NLRP3 Inflammasome Pathways. Non-canonical NLRP3 inflammasome activation (left) is induced by LPS internalization into the cytosol by transfection or infection. Caspase-11/4/5 induces pyroptosis through the cleavage of GSDMD. This process also activates pannexin-1 through caspase-11 to release ATP and induce K⁺ efflux, which drives NLRP3 inflammasome assembly and release of IL-1β. The alternative NLRP3 inflammasome (right) is activated in human monocytes in response to LPS and requires receptor-interacting serine/threonine-protein kinase 1 (RIPK1), FADD, and caspase-8 for its activation. This pathway is K⁺ efflux independent and does not induce pyroptosis.