Publications

Detailed Information

Identification of the PANoptosome: A Molecular Platform Triggering Pyroptosis, Apoptosis, and Necroptosis (PANoptosis)

Cited 212 time in Web of Science Cited 231 time in Scopus
Authors

Christgen, Shelbi; Zheng, Min; Kesavardhana, Sannula; Karki, Rajendra; Malireddi, R. K. Subbarao; Banoth, Balaji; Place, David E.; Briard, Benoit; Sharma, Bhesh Raj; Tuladhar, Shraddha; Samir, Parimal; Burton, Amanda; Kanneganti, Thirumala-Devi

Issue Date
2020-05
Publisher
Frontiers Media S.A.
Citation
Frontiers in cellular and infection microbiology, Vol.10, p. 237
Abstract
Programmed cell death plays crucial roles in organismal development and host defense. Recent studies have highlighted mechanistic overlaps and extensive, multifaceted crosstalk between pyroptosis, apoptosis, and necroptosis, three programmed cell death pathways traditionally considered autonomous. The growing body of evidence, in conjunction with the identification of molecules controlling the concomitant activation of all three pathways by pathological triggers, has led to the development of the concept of PANoptosis. During PANoptosis, inflammatory cell death occurs through the collective activation of pyroptosis, apoptosis, and necroptosis, which can circumvent pathogen-mediated inhibition of individual death pathways. Many of the molecular details of this emerging pathway are unclear. Here, we describe the activation of PANoptosis by bacterial and viral triggers and report protein interactions that reveal the formation of a PANoptosome complex. Infection of macrophages with influenza A virus, vesicular stomatitis virus,Listeria monocytogenes, orSalmonella entericaserovar Typhimurium resulted in robust cell death and the hallmarks of PANoptosis activation. Combined deletion of the PANoptotic components caspase-1 (CASP1), CASP11, receptor-interacting serine/threonine-protein kinase 3 (RIPK3), and CASP8 largely protected macrophages from cell death induced by these pathogens, while deletion of individual components provided reduced or no protection. Further, molecules from the pyroptotic, apoptotic, and necroptotic cell death pathways interacted to form a single molecular complex that we have termed the PANoptosome. Overall, our study identifies pathogens capable of activating PANoptosis and the formation of a PANoptosome complex.
ISSN
2235-2988
URI
https://hdl.handle.net/10371/203013
DOI
https://doi.org/10.3389/fcimb.2020.00237
Files in This Item:
There are no files associated with this item.
Appears in Collections:

Related Researcher

  • College of Natural Sciences
  • School of Biological Sciences
Research Area Cytokine Storm, Host Defense, Innate Immunity in Metabolic and Inflammatory Diseases

Altmetrics

Item View & Download Count

  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Share