Research ArticleCELL DEATH

Noncanonical inflammasome signaling elicits gasdermin D–dependent neutrophil extracellular traps

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Science Immunology  24 Aug 2018:
Vol. 3, Issue 26, eaar6676
DOI: 10.1126/sciimmunol.aar6676

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Casting NETs

Gasdermin D (GSDMD), a pore-forming protein, has emerged a key downstream effector in pyroptosis, a form of cell death induced by intracellular lipopolysaccharide (LPS). Here, by examining the role of GSDMD in the neutrophil response to LPS and cytosolic Gram-negative bacteria, Chen et al. have uncovered an important role for GSDMD in the generation of neutrophil extracellular traps (NETs). NETs are composed of chromatin and antimicrobial proteins and are cast by dying neutrophils in a process termed NETosis. The authors report that GSDMD is directly cleaved by caspase-11 and that intracellular LPS–induced NETosis is dependent on both caspase-11 and GSDMD. In the same issue, Sollberger et al. also report a role for GSDMD in NETosis.