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Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA
Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-a...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760655/ https://www.ncbi.nlm.nih.gov/pubmed/29317705 http://dx.doi.org/10.1038/s41598-017-18468-7 |
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author | Nerlich, Andreas Mieth, Maren Letsiou, Eleftheria Fatykhova, Diana Zscheppang, Katja Imai-Matsushima, Aki Meyer, Thomas F. Paasch, Lisa Mitchell, Timothy J. Tönnies, Mario Bauer, Torsten T. Schneider, Paul Neudecker, Jens Rückert, Jens C. Eggeling, Stephan Schimek, Maria Witzenrath, Martin Suttorp, Norbert Hippenstiel, Stefan Hocke, Andreas C. |
author_facet | Nerlich, Andreas Mieth, Maren Letsiou, Eleftheria Fatykhova, Diana Zscheppang, Katja Imai-Matsushima, Aki Meyer, Thomas F. Paasch, Lisa Mitchell, Timothy J. Tönnies, Mario Bauer, Torsten T. Schneider, Paul Neudecker, Jens Rückert, Jens C. Eggeling, Stephan Schimek, Maria Witzenrath, Martin Suttorp, Norbert Hippenstiel, Stefan Hocke, Andreas C. |
author_sort | Nerlich, Andreas |
collection | PubMed |
description | Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-associated molecular patterns (DAMP). To test this hypothesis, we established a novel live-cell imaging based assay to analyse mitochondrial function and associated release of mitochondrial DNA (mtDNA) as DAMP in real-time. We first revealed that bacterially released PLY caused significant changes of the cellular ATP homeostasis and led to morphologic alterations of mitochondria in human alveolar epithelial cells in vitro and, by use of spectral live-tissue imaging, in human alveoli. This was accompanied by strong mitochondrial calcium influx and loss of mitochondrial membrane potential resulting in opening of the mitochondrial permeability transition pore and mtDNA release without activation of intrinsic apoptosis. Moreover, our data indicate cellular mtDNA liberation via microvesicles, which may contribute to S.pn. related pro-inflammatory immune activation in the human alveolar compartment. |
format | Online Article Text |
id | pubmed-5760655 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57606552018-01-17 Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA Nerlich, Andreas Mieth, Maren Letsiou, Eleftheria Fatykhova, Diana Zscheppang, Katja Imai-Matsushima, Aki Meyer, Thomas F. Paasch, Lisa Mitchell, Timothy J. Tönnies, Mario Bauer, Torsten T. Schneider, Paul Neudecker, Jens Rückert, Jens C. Eggeling, Stephan Schimek, Maria Witzenrath, Martin Suttorp, Norbert Hippenstiel, Stefan Hocke, Andreas C. Sci Rep Article Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-associated molecular patterns (DAMP). To test this hypothesis, we established a novel live-cell imaging based assay to analyse mitochondrial function and associated release of mitochondrial DNA (mtDNA) as DAMP in real-time. We first revealed that bacterially released PLY caused significant changes of the cellular ATP homeostasis and led to morphologic alterations of mitochondria in human alveolar epithelial cells in vitro and, by use of spectral live-tissue imaging, in human alveoli. This was accompanied by strong mitochondrial calcium influx and loss of mitochondrial membrane potential resulting in opening of the mitochondrial permeability transition pore and mtDNA release without activation of intrinsic apoptosis. Moreover, our data indicate cellular mtDNA liberation via microvesicles, which may contribute to S.pn. related pro-inflammatory immune activation in the human alveolar compartment. Nature Publishing Group UK 2018-01-09 /pmc/articles/PMC5760655/ /pubmed/29317705 http://dx.doi.org/10.1038/s41598-017-18468-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Nerlich, Andreas Mieth, Maren Letsiou, Eleftheria Fatykhova, Diana Zscheppang, Katja Imai-Matsushima, Aki Meyer, Thomas F. Paasch, Lisa Mitchell, Timothy J. Tönnies, Mario Bauer, Torsten T. Schneider, Paul Neudecker, Jens Rückert, Jens C. Eggeling, Stephan Schimek, Maria Witzenrath, Martin Suttorp, Norbert Hippenstiel, Stefan Hocke, Andreas C. Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA |
title | Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA |
title_full | Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA |
title_fullStr | Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA |
title_full_unstemmed | Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA |
title_short | Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA |
title_sort | pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial dna |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760655/ https://www.ncbi.nlm.nih.gov/pubmed/29317705 http://dx.doi.org/10.1038/s41598-017-18468-7 |
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