IMMUNOLOGY2025™ Conference Recordings-Fanning the flames: pyroptosis in infection, cancer and neurodegeneration

Fanning the flames: pyroptosis in infection, cancer and neurodegeneration - Judy Lieberman

Video Transcription

Video Summary

The talk described recent research on pyroptosis, a highly inflammatory form of cell death driven by gasdermin proteins. The speaker explained how the innate immune system detects pathogens and danger signals through surface and cytosolic sensors, with inflammasomes activating inflammatory caspases that cleave gasdermins. The gasdermin N-terminal fragment forms membrane pores, releasing cytokines such as IL-1 and other inflammatory molecules.<br /><br />The lab’s work showed that gasdermin D rapidly damages mitochondria, especially through recognition of cardiolipin, making pyroptosis one of the fastest cell death pathways. They also found that gasdermin D can directly kill bacteria, suggesting possible antibiotic-like properties. The speaker discussed therapeutic efforts to block pyroptosis, including the drug disulfiram, which reduced inflammation and improved survival in mouse models of sepsis.<br /><br />The talk then highlighted disease relevance. In severe COVID-19, monocytes and macrophages undergo pyroptosis after antibody-mediated viral uptake, contributing to cytokine storm and tissue damage. Gasdermin E, normally linked to apoptosis, can switch tumor cell death into immunogenic pyroptosis, boosting anti-tumor immunity and improving tumor control in mice. Finally, gasdermin E was shown to contribute to neurodegeneration, including ALS, by damaging mitochondria in neurons. Overall, the speaker emphasized that gasdermins and pyroptosis are important in infection, cancer, and neurodegenerative disease.

Keywords

pyroptosis

gasdermin

inflammasome

caspase

IL-1

sepsis

COVID-19

neurodegeneration