Holley et al. investigated the morphological changes during pyroptotic cell death, and identified that inflammasome activation induces F-actin-rich filopodia formation before plasma membrane rupture. Gasdermin D pores facilitate calcium influx, triggering actin polymerization and crowning of the resultant corpse with filopodia. Conventional dendritic cells recognize pyroptotic filopodia through the F-actin receptor, CLEC9A. This recognition triggered signaling via spleen tyrosine kinase (SYK), essential for antigen cross-presentation to T cells, promoting the transition from innate to adaptive immune response.
Contributed by Shishir Pant
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(1,2).
Author Info: (1) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. Max Planck Institute for Infection Biology, Berlin, Germany. (2) Institute for Mo
Author Info: (1) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. Max Planck Institute for Infection Biology, Berlin, Germany. (2) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. m.monteleone@imb.uq.edu.au. (3) Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. (4) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia. (5) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia. (6) Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. (7) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. (8) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. (9) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. (10) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. (11) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. (12) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. Faculty of Science, University of Queensland, Brisbane, Queensland, Australia. (13) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. (14) Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia. (15) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. (16) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. (17) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia. (18) Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. (19) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. (20) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. (21) Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. K.Schroder@imb.uq.edu.au.
