Flexible Usage and Interconnectivity of Diverse Cell Death Pathways Protect against Intracellular Infection
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UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2020-09-15Keywords
Salmonellaapoptosis
caspase-1
caspase-11
caspase-8
cell death
effector caspases
gasdermin D
necroptosis
pyroptosis
Amino Acids, Peptides, and Proteins
Bacteria
Bacterial Infections and Mycoses
Cell Biology
Cellular and Molecular Physiology
Enzymes and Coenzymes
Immunity
Immunology of Infectious Disease
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Show full item recordAbstract
Programmed cell death contributes to host defense against pathogens. To investigate the relative importance of pyroptosis, necroptosis, and apoptosis during Salmonella infection, we infected mice and macrophages deficient for diverse combinations of caspases-1, -11, -12, and -8 and receptor interacting serine/threonine kinase 3 (RIPK3). Loss of pyroptosis, caspase-8-driven apoptosis, or necroptosis had minor impact on Salmonella control. However, combined deficiency of these cell death pathways caused loss of bacterial control in mice and their macrophages, demonstrating that host defense can employ varying components of several cell death pathways to limit intracellular infections. This flexible use of distinct cell death pathways involved extensive cross-talk between initiators and effectors of pyroptosis and apoptosis, where initiator caspases-1 and -8 also functioned as executioners when all known effectors of cell death were absent. These findings uncover a highly coordinated and flexible cell death system with in-built fail-safe processes that protect the host from intracellular infections.Source
Doerflinger M, Deng Y, Whitney P, Salvamoser R, Engel S, Kueh AJ, Tai L, Bachem A, Gressier E, Geoghegan ND, Wilcox S, Rogers KL, Garnham AL, Dengler MA, Bader SM, Ebert G, Pearson JS, De Nardo D, Wang N, Yang C, Pereira M, Bryant CE, Strugnell RA, Vince JE, Pellegrini M, Strasser A, Bedoui S, Herold MJ. Flexible Usage and Interconnectivity of Diverse Cell Death Pathways Protect against Intracellular Infection. Immunity. 2020 Sep 15;53(3):533-547.e7. doi: 10.1016/j.immuni.2020.07.004. Epub 2020 Jul 30. PMID: 32735843; PMCID: PMC7500851. Link to article on publisher's site
DOI
10.1016/j.immuni.2020.07.004Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41569PubMed ID
32735843Notes
Full author list omitted for brevity. For the full list of authors, see article.
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Copyright 2020. The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.immuni.2020.07.004
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Except where otherwise noted, this item's license is described as Copyright 2020. The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).