Fig. 5. Triggers and molecules involved in PANoptosome assembly.

Pathogens such as IAV, HSV1, Francisella, and Yersinia and other agents such as IFN + KPT and TNF + IFNγ have been identified to induce PANoptosis. ZBP1 senses IAV or endogenous Z-NA to assemble ZBP1 PANoptosomes consisting of ZBP1 and other cell death molecules. CASP6 potentiates the interaction between RIPK3 and ZBP1. AIM2 senses dsDNA during HSV1 or Francisella infection to assemble the AIM2 PANoptosome. TNF + IFNγ activates STAT1 to induce IRF1-dependent NO release, which activates CASP8 and RIPK3 to trigger PANoptosis. During Yersinia infection, RIPK1 assembles the RIPK1 PANoptosome.