NET formation is independent of gasdermin D and pyroptotic cell death.

Stojkov, Darko; Claus, Meike J; Kozlowski, Evelyne; Oberson, Kevin; Schaeren, Olivier P; Benarafa, Charaf; Yousefi, Shida; Simon, Hans-Uwe (2023). NET formation is independent of gasdermin D and pyroptotic cell death. Science signaling, 16(769), eabm0517. American Association for the Advancement of Science 10.1126/scisignal.abm0517

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Neutrophil extracellular traps (NETs) are DNA scaffolds coated with granule proteins that are released by neutrophils to ensnare and kill bacteria. NET formation occurs in response to many stimuli through independent molecular pathways. Although NET release has been equated to a form of lytic cell death, live neutrophils can rapidly release antimicrobial NETs. Gasdermin D (GSDMD), which causes pyroptotic death in macrophages, is thought to be required for NET formation by neutrophils. Through experiments with known physiological activators of NET formation and ligands that activate canonical and noncanonical inflammasome signaling pathways, we demonstrated that Gsdmd-deficient mouse neutrophils were as competent as wild-type mouse neutrophils in producing NETs. Furthermore, GSDMD was not cleaved in wild-type neutrophils during NET release in response to inflammatory mediators. We found that activation of both canonical and noncanonical inflammasome signaling pathways resulted in GSDMD cleavage in wild-type neutrophils but was not associated with cell death. Moreover, NET formation as a result of either pathway of inflammasome activation did not require GSDMD. Together, these data suggest that NETs can be formed by viable neutrophils after inflammasome activation and that this function does not require GSDMD.

Item Type:	Journal Article (Original Article)
Division/Institute:	09 Interdisciplinary Units > Microscopy Imaging Center (MIC) 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology 04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases 05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
UniBE Contributor:	Stojkov, Darko, Claus, Meike Janina, Kozlowski, Eveline, Oberson, Kevin, Schären, Olivier Pascal, Benarafa, Charaf, Yousefi, Shida, Simon, Hans-Uwe
Subjects:	600 Technology > 610 Medicine & health 600 Technology > 630 Agriculture 500 Science > 570 Life sciences; biology
ISSN:	1937-9145
Publisher:	American Association for the Advancement of Science
Language:	English
Submitter:	Pubmed Import
Date Deposited:	30 Jan 2023 12:46
Last Modified:	19 Sep 2024 15:48
Publisher DOI:	10.1126/scisignal.abm0517
PubMed ID:	36693132
URI:	https://boris.unibe.ch/id/eprint/177861