Fig. 10

Schematic representation of E. histolytica-macrophage interaction and induction of caspase-4 and -1 activation and IL-1β release. The first step of caspase activation is Eh adherence to macrophage contact via the Gal-lectin adhesin that binds to Gal/GalNAc residues on the macrophage surfaces (1). EhCP5 is a cysteine protease that is highly expressed on the surface of Eh and was shown to activate both caspase-4 and -1 (2). EhCP5 binds to α₅β₁ integrin on macrophage surface to trigger ATP release through pannexin-1 channel and subsequently signals back onto the P2X₇ receptor to activate the NLRP3 inflammasome. Simultaneously, K⁺ efflux and the generation of reactive oxygen species converge to activate the NLRP3 inflammasome and it also activates caspase-4 (3, boxed out). Caspase-4 is simultaneously activated with caspase-1 and caspase-4 enhances caspase-1 activity by cleaving the caspase-1 CARD domains independent of the inflammasome complex (4). Both caspase-4 and -1 cleaves GSDMD (5) to induce IL-1β release (6)