Oral Presentation The 16th Australian Peptide Conference 2025

Die hard: cell explosion by pyroptosis escalates immune responses (130903)

Kate Schroder 1
  1. Institute for Molecular Bioscience, St Lucia, QLD, Australia

Inflammasomes induce pyroptosis and, through poorly defined mechanisms, promote adaptive immune responses. Little is known of the structural architecture of cells undergoing pyroptosis, and whether pyroptotic corpses are immunogenic. Here, we show that inflammasomes trigger the GSDMD- and calcium-dependent eruption of filopodia from the plasma membrane minutes before cell rupture, to crown the resultant corpse with filopodia. As a rich store of F-actin, pyroptotic filopodia are recognised by dendritic cells through the F-actin receptor, CLEC9A (DNGR1). We propose that cells assemble filopodia before cell rupture to serve as a posthumous mark for a cell that has died by gasdermin-induced pyroptosis, or MLKL-induced necroptosis, for recognition by dendritic cells. This study reveals the spectacular morphology of pyroptosis and identifies a mechanism by which inflammasomes induce pyroptotic cells to construct a de novo alarmin that activates dendritic cells via CLEC9A, which co-ordinates the transition from innate to adaptive immunity.