AI Article Synopsis

  • Apoptosis leads to cell dismantling for immune silence, while pyroptosis causes inflammation and has poorly understood cell structures and immunogenicity.
  • The study discovers that inflammasomes trigger the release of filopodia from cells minutes before they undergo pyroptosis, effectively marking the dead cells with these projections.
  • Pyroptotic filopodia, rich in F-actin, are identified by dendritic cells through the receptor CLEC9A, suggesting a method for these immune cells to recognize and respond to pyroptotic and necroptotic cell death in the immune system.

Article Abstract

While apoptosis dismantles the cell to enforce immunological silence, pyroptotic cell death provokes inflammation. Little is known of the structural architecture of cells undergoing pyroptosis, and whether pyroptotic corpses are immunogenic. Here we report that inflammasomes trigger the Gasdermin-D- and calcium-dependent eruption of filopodia from the plasma membrane minutes before pyroptotic cell rupture, to crown the resultant corpse with filopodia. As a rich store of F-actin, pyroptotic filopodia are recognized 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 coordinates the transition from innate to adaptive immunity.

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Source
http://dx.doi.org/10.1038/s41590-024-02024-3DOI Listing

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