Pyroptosis: host cell death and inflammation

Microorganism- and host-derived signals can stimulate formation of a multiprotein complex called the inflammasome, which activates the cysteine protease caspase 1. In turn, caspase 1 triggers an inflammatory programmed cell death pathway known as pyroptosis. Numerous pathogens have evolved a mechanism to subvert pyroptosis and persist within infected cells. Eukaryotic cells can initiate several distinct programmes of self-destruction, and the nature of the cell death process (non-inflammatory or proinflammatory) instructs responses of neighbouring cells, which in turn dictates important systemic physiological outcomes. Pyroptosis, or caspase 1-dependent cell death, is inherently inflammatory, is triggered by various pathological stimuli, such as stroke, heart attack or cancer, and is crucial for controlling microbial infections. Pathogens have evolved mechanisms to inhibit pyroptosis, enhancing their ability to persist and cause disease. Ultimately, there is a competition between host and pathogen to regulate pyroptosis, and the outcome dictates life or death of the host.