Fig. 11

Pyrin inflammasome. Under basal conditions, human and murine pyrin proteins are phosphorylated by the RhoA effector kinase PKN1/2 and bind to 14-3-3 proteins, maintaining them in an inactive state. Bacterial toxins, including Clostridium difficile TcdA and TcdB, inhibit RhoA activity and downstream PKN1/2-mediated phosphorylation, resulting in pyrin dephosphorylation and dissociation from 14-3-3 proteins. Activated pyrin then recruits ASC and caspase-1 to assemble a functional inflammasome complex