Pyrin,encoded by MEFV gene,is conserved in humans and mice.Mutations in the MEFV gene are associated with the human autoinflammatory disease familial Mediterranean fever(FMF).Pyrin can interact with the inflammasome adaptor ASC and induce inflammatory caspase-1 activation in monocytic cells,but the physiological function of Pyrin has been unknown for many years.Here we summarize previous studies of Pyrin function under the context of FMF and immunity,and discuss a recent study demonstrating that Pyrin forms an inflammasome complex for caspase-1 activation in innate immunity.Pyrin inflammasome detects inactivating modifications of host Rho GTPases by diverse bacterial toxins and infections,including Clostridium difficile glucosylating cytotoxin Tcd B,FIC-domain adenylyltransferase effectors from Vibrio parahaemolyticus and Histophilus somni,ADP-ribosylating Clostridium botulinum C3 toxin as well as Burkholderia cenocepacia infection.The mode of Pyrin action,i.e.,sensing pathogen virulence activity rather than directly recognizing a microbial molecule,represents a new paradigm in innate immunity.
