Fig. 5: Proposed schematic model for the suppression of PANoptosis by EseJ.
From: T3SS effector EseJ in Edwardsiella piscicida inhibits PANoptosis in macrophages
The E. piscicida T3SS protein EseJ controls the conversion from apoptotic cell rounding to PANoptotic cell lysis through activating TAK1. The EseJ protein suppresses apoptosis by down regulating type 1 fimbriae, which would otherwise interact with host cell receptors to activate caspase-8 mediated extrinsic apoptosis21. Upon being internalized, EseJ translocated by T3SS stimulates TAK1 phosphorylation and inhibits the assembly of NLRP3-caspase-8-RIPK1 PANoptosome, thereby (1) suppressing GSDMD cleavage, GSDMD pore formation and pyroptosis; (2) inhibiting caspase-3 activation and apoptosis; (3) deactivating MLKL phosphorylation, MLKL pore formation and necroptosis. The E. piscicida T3SS protein EseJ controls the transition from apoptotic cell rounding to PANoptotic cell lysis by activating TAK1.
