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Necroptotic debris including damaged mitochondria elicits sepsis-like syndrome during late-phase tularemia
Infection with Francisella tularensis ssp. tularensis (Ft) strain SchuS4 causes an often lethal disease known as tularemia in rodents, non-human primates, and humans. Ft subverts host cell death programs to facilitate their exponential replication within macrophages and other cell types during early...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5611684/ https://www.ncbi.nlm.nih.gov/pubmed/28955505 http://dx.doi.org/10.1038/cddiscovery.2017.56 |
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author | Singh, Anju Periasamy, Sivakumar Malik, Meenakshi Bakshi, Chandra Shekhar Stephen, Laurie Ault, Jeffrey G Mannella, Carmen A Sellati, Timothy J |
author_facet | Singh, Anju Periasamy, Sivakumar Malik, Meenakshi Bakshi, Chandra Shekhar Stephen, Laurie Ault, Jeffrey G Mannella, Carmen A Sellati, Timothy J |
author_sort | Singh, Anju |
collection | PubMed |
description | Infection with Francisella tularensis ssp. tularensis (Ft) strain SchuS4 causes an often lethal disease known as tularemia in rodents, non-human primates, and humans. Ft subverts host cell death programs to facilitate their exponential replication within macrophages and other cell types during early respiratory infection (⩽72 h). The mechanism(s) by which cell death is triggered remains incompletely defined, as does the impact of Ft on mitochondria, the host cell’s organellar ‘canary in a coal mine’. Herein, we reveal that Ft infection of host cells, particularly macrophages and polymorphonuclear leukocytes, drives necroptosis via a receptor-interacting protein kinase 1/3-mediated mechanism. During necroptosis mitochondria and other organelles become damaged. Ft-induced mitochondrial damage is characterized by: (i) a decrease in membrane potential and consequent mitochondrial oncosis or swelling, (ii) increased generation of superoxide radicals, and (iii) release of intact or damaged mitochondria into the lung parenchyma. Host cell recognition of and response to released mitochondria and other damage-associated molecular patterns engenders a sepsis-like syndrome typified by production of TNF, IL-1β, IL-6, IL-12p70, and IFN-γ during late-phase tularemia (⩾72 h), but are absent early during infection. |
format | Online Article Text |
id | pubmed-5611684 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-56116842017-09-27 Necroptotic debris including damaged mitochondria elicits sepsis-like syndrome during late-phase tularemia Singh, Anju Periasamy, Sivakumar Malik, Meenakshi Bakshi, Chandra Shekhar Stephen, Laurie Ault, Jeffrey G Mannella, Carmen A Sellati, Timothy J Cell Death Discov Article Infection with Francisella tularensis ssp. tularensis (Ft) strain SchuS4 causes an often lethal disease known as tularemia in rodents, non-human primates, and humans. Ft subverts host cell death programs to facilitate their exponential replication within macrophages and other cell types during early respiratory infection (⩽72 h). The mechanism(s) by which cell death is triggered remains incompletely defined, as does the impact of Ft on mitochondria, the host cell’s organellar ‘canary in a coal mine’. Herein, we reveal that Ft infection of host cells, particularly macrophages and polymorphonuclear leukocytes, drives necroptosis via a receptor-interacting protein kinase 1/3-mediated mechanism. During necroptosis mitochondria and other organelles become damaged. Ft-induced mitochondrial damage is characterized by: (i) a decrease in membrane potential and consequent mitochondrial oncosis or swelling, (ii) increased generation of superoxide radicals, and (iii) release of intact or damaged mitochondria into the lung parenchyma. Host cell recognition of and response to released mitochondria and other damage-associated molecular patterns engenders a sepsis-like syndrome typified by production of TNF, IL-1β, IL-6, IL-12p70, and IFN-γ during late-phase tularemia (⩾72 h), but are absent early during infection. Nature Publishing Group 2017-09-25 /pmc/articles/PMC5611684/ /pubmed/28955505 http://dx.doi.org/10.1038/cddiscovery.2017.56 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Singh, Anju Periasamy, Sivakumar Malik, Meenakshi Bakshi, Chandra Shekhar Stephen, Laurie Ault, Jeffrey G Mannella, Carmen A Sellati, Timothy J Necroptotic debris including damaged mitochondria elicits sepsis-like syndrome during late-phase tularemia |
title | Necroptotic debris including damaged mitochondria elicits sepsis-like syndrome during late-phase tularemia |
title_full | Necroptotic debris including damaged mitochondria elicits sepsis-like syndrome during late-phase tularemia |
title_fullStr | Necroptotic debris including damaged mitochondria elicits sepsis-like syndrome during late-phase tularemia |
title_full_unstemmed | Necroptotic debris including damaged mitochondria elicits sepsis-like syndrome during late-phase tularemia |
title_short | Necroptotic debris including damaged mitochondria elicits sepsis-like syndrome during late-phase tularemia |
title_sort | necroptotic debris including damaged mitochondria elicits sepsis-like syndrome during late-phase tularemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5611684/ https://www.ncbi.nlm.nih.gov/pubmed/28955505 http://dx.doi.org/10.1038/cddiscovery.2017.56 |
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