Description:

Department of Microbiology-Immunology Seminar Series

“Sounding the Alarm and Putting Out the Fire:
New Mechanistic Insights into Immunity to Invasive Infection”

Judy Lieberman, MD, PhD / Harvard University

Description:

Recently we identified the mechanism responsible for pyroptosis, the inflammatory death triggered by inflammasome activation in response to invasive infections and danger signals. Pyroptosis and inflammatory cytokine release is mediated by pore formation by the N-terminal fragment of gasdermin D after gasdermin D is cleaved by inflammatory caspases. We also showed that this gasdermin fragment binds to and permeabilizes the membranes of intracellular bacteria, killing the very bacteria that trigger the inflammasome. Moreover the active fragment is released during pyroptosis and kills extracellular bacteria, but not bystander mammalian cells. Recent work has solved the structure of the gasdermin D pore assembled during pyroptosis and identified inhibitors of pore formation that might be useful for treating sepsis and inflammatory/autoimmune diseases.