Pyroptosis, an inflammatory form of cell death, is caused by gasdermin pores in the cell membrane. These form when activated caspases cleave the pore-forming N-terminal fragment of gasdermin D (GSDMD) from the autoinhibitory C-terminal fragment. Although pyroptosis is important for antimicrobial and anti-tumour immunity, it can also trigger excessive inflammation. A study in Cell now demonstrates that GSDMD pores can be transplanted from cell to cell via extracellular vesicles (EVs) and cause death of bystander cells.

Wright et al. investigated the nature of bystander pyroptosis using in vitro and in vivo models and engineered cells in which pyroptosis can be induced with doxycycline. Intercellular propagation of pyroptosis was found to be contact independent, but instead transferred by EVs from pyroptotic cells. Super-resolution microscopy showed that GSDMD is present in the pore conformation on EVs and that pre-existing pores can be transferred to the recipient cell surface without cellular uptake of the EV.