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An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages
Pyroptosis has emerged as a key mechanism by which inflammasomes promote host defense against microbial pathogens and sterile inflammation. Gasdermin D (GSDMD)-mediated cell lysis is a hallmark of pyroptosis, but our understanding of cell death signaling during pyroptosis is fragmented. Here, we sho...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408007/ https://www.ncbi.nlm.nih.gov/pubmed/32726624 http://dx.doi.org/10.1016/j.celrep.2020.107959 |
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author | de Vasconcelos, Nathalia Moraes Van Opdenbosch, Nina Van Gorp, Hanne Martín-Pérez, Rosa Zecchin, Annalisa Vandenabeele, Peter Lamkanfi, Mohamed |
author_facet | de Vasconcelos, Nathalia Moraes Van Opdenbosch, Nina Van Gorp, Hanne Martín-Pérez, Rosa Zecchin, Annalisa Vandenabeele, Peter Lamkanfi, Mohamed |
author_sort | de Vasconcelos, Nathalia Moraes |
collection | PubMed |
description | Pyroptosis has emerged as a key mechanism by which inflammasomes promote host defense against microbial pathogens and sterile inflammation. Gasdermin D (GSDMD)-mediated cell lysis is a hallmark of pyroptosis, but our understanding of cell death signaling during pyroptosis is fragmented. Here, we show that independently of GSDMD-mediated plasma membrane permeabilization, inflammasome receptors engage caspase-1 and caspase-8, both of which redundantly promote activation of apoptotic executioner caspase-3 and caspase-7 in pyroptotic macrophages. Impaired GSDMD pore formation downstream of caspase-1 and caspase-8 activation suffices to unmask the apoptotic phenotype of pyroptotic macrophages. Combined inactivation of initiator caspase-1 and caspase-8, or executioner caspase-3 and caspase-7, is required to abolish inflammasome-induced DEVDase activity during pyroptosis and in apoptotic Gsdmd(−/−) cells. Collectively, these results unveil a robust apoptotic caspase network that is activated in parallel to GSDMD-mediated plasma membrane permeabilization and safeguards cell death induction in pyroptotic macrophages. |
format | Online Article Text |
id | pubmed-7408007 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-74080072020-08-12 An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages de Vasconcelos, Nathalia Moraes Van Opdenbosch, Nina Van Gorp, Hanne Martín-Pérez, Rosa Zecchin, Annalisa Vandenabeele, Peter Lamkanfi, Mohamed Cell Rep Article Pyroptosis has emerged as a key mechanism by which inflammasomes promote host defense against microbial pathogens and sterile inflammation. Gasdermin D (GSDMD)-mediated cell lysis is a hallmark of pyroptosis, but our understanding of cell death signaling during pyroptosis is fragmented. Here, we show that independently of GSDMD-mediated plasma membrane permeabilization, inflammasome receptors engage caspase-1 and caspase-8, both of which redundantly promote activation of apoptotic executioner caspase-3 and caspase-7 in pyroptotic macrophages. Impaired GSDMD pore formation downstream of caspase-1 and caspase-8 activation suffices to unmask the apoptotic phenotype of pyroptotic macrophages. Combined inactivation of initiator caspase-1 and caspase-8, or executioner caspase-3 and caspase-7, is required to abolish inflammasome-induced DEVDase activity during pyroptosis and in apoptotic Gsdmd(−/−) cells. Collectively, these results unveil a robust apoptotic caspase network that is activated in parallel to GSDMD-mediated plasma membrane permeabilization and safeguards cell death induction in pyroptotic macrophages. Cell Press 2020-07-28 /pmc/articles/PMC7408007/ /pubmed/32726624 http://dx.doi.org/10.1016/j.celrep.2020.107959 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article de Vasconcelos, Nathalia Moraes Van Opdenbosch, Nina Van Gorp, Hanne Martín-Pérez, Rosa Zecchin, Annalisa Vandenabeele, Peter Lamkanfi, Mohamed An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages |
title | An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages |
title_full | An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages |
title_fullStr | An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages |
title_full_unstemmed | An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages |
title_short | An Apoptotic Caspase Network Safeguards Cell Death Induction in Pyroptotic Macrophages |
title_sort | apoptotic caspase network safeguards cell death induction in pyroptotic macrophages |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408007/ https://www.ncbi.nlm.nih.gov/pubmed/32726624 http://dx.doi.org/10.1016/j.celrep.2020.107959 |
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