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The Zebrafish as a New Model for the In Vivo Study of Shigella flexneri Interaction with Phagocytes and Bacterial Autophagy
Autophagy, an ancient and highly conserved intracellular degradation process, is viewed as a critical component of innate immunity because of its ability to deliver cytosolic bacteria to the lysosome. However, the role of bacterial autophagy in vivo remains poorly understood. The zebrafish (Danio re...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764221/ https://www.ncbi.nlm.nih.gov/pubmed/24039575 http://dx.doi.org/10.1371/journal.ppat.1003588 |
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author | Mostowy, Serge Boucontet, Laurent Mazon Moya, Maria J. Sirianni, Andrea Boudinot, Pierre Hollinshead, Michael Cossart, Pascale Herbomel, Philippe Levraud, Jean-Pierre Colucci-Guyon, Emma |
author_facet | Mostowy, Serge Boucontet, Laurent Mazon Moya, Maria J. Sirianni, Andrea Boudinot, Pierre Hollinshead, Michael Cossart, Pascale Herbomel, Philippe Levraud, Jean-Pierre Colucci-Guyon, Emma |
author_sort | Mostowy, Serge |
collection | PubMed |
description | Autophagy, an ancient and highly conserved intracellular degradation process, is viewed as a critical component of innate immunity because of its ability to deliver cytosolic bacteria to the lysosome. However, the role of bacterial autophagy in vivo remains poorly understood. The zebrafish (Danio rerio) has emerged as a vertebrate model for the study of infections because it is optically accessible at the larval stages when the innate immune system is already functional. Here, we have characterized the susceptibility of zebrafish larvae to Shigella flexneri, a paradigm for bacterial autophagy, and have used this model to study Shigella-phagocyte interactions in vivo. Depending on the dose, S. flexneri injected in zebrafish larvae were either cleared in a few days or resulted in a progressive and ultimately fatal infection. Using high resolution live imaging, we found that S. flexneri were rapidly engulfed by macrophages and neutrophils; moreover we discovered a scavenger role for neutrophils in eliminating infected dead macrophages and non-immune cell types that failed to control Shigella infection. We observed that intracellular S. flexneri could escape to the cytosol, induce septin caging and be targeted to autophagy in vivo. Depletion of p62 (sequestosome 1 or SQSTM1), an adaptor protein critical for bacterial autophagy in vitro, significantly increased bacterial burden and host susceptibility to infection. These results show the zebrafish larva as a new model for the study of S. flexneri interaction with phagocytes, and the manipulation of autophagy for anti-bacterial therapy in vivo. |
format | Online Article Text |
id | pubmed-3764221 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37642212013-09-13 The Zebrafish as a New Model for the In Vivo Study of Shigella flexneri Interaction with Phagocytes and Bacterial Autophagy Mostowy, Serge Boucontet, Laurent Mazon Moya, Maria J. Sirianni, Andrea Boudinot, Pierre Hollinshead, Michael Cossart, Pascale Herbomel, Philippe Levraud, Jean-Pierre Colucci-Guyon, Emma PLoS Pathog Research Article Autophagy, an ancient and highly conserved intracellular degradation process, is viewed as a critical component of innate immunity because of its ability to deliver cytosolic bacteria to the lysosome. However, the role of bacterial autophagy in vivo remains poorly understood. The zebrafish (Danio rerio) has emerged as a vertebrate model for the study of infections because it is optically accessible at the larval stages when the innate immune system is already functional. Here, we have characterized the susceptibility of zebrafish larvae to Shigella flexneri, a paradigm for bacterial autophagy, and have used this model to study Shigella-phagocyte interactions in vivo. Depending on the dose, S. flexneri injected in zebrafish larvae were either cleared in a few days or resulted in a progressive and ultimately fatal infection. Using high resolution live imaging, we found that S. flexneri were rapidly engulfed by macrophages and neutrophils; moreover we discovered a scavenger role for neutrophils in eliminating infected dead macrophages and non-immune cell types that failed to control Shigella infection. We observed that intracellular S. flexneri could escape to the cytosol, induce septin caging and be targeted to autophagy in vivo. Depletion of p62 (sequestosome 1 or SQSTM1), an adaptor protein critical for bacterial autophagy in vitro, significantly increased bacterial burden and host susceptibility to infection. These results show the zebrafish larva as a new model for the study of S. flexneri interaction with phagocytes, and the manipulation of autophagy for anti-bacterial therapy in vivo. Public Library of Science 2013-09-05 /pmc/articles/PMC3764221/ /pubmed/24039575 http://dx.doi.org/10.1371/journal.ppat.1003588 Text en © 2013 Mostowy et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mostowy, Serge Boucontet, Laurent Mazon Moya, Maria J. Sirianni, Andrea Boudinot, Pierre Hollinshead, Michael Cossart, Pascale Herbomel, Philippe Levraud, Jean-Pierre Colucci-Guyon, Emma The Zebrafish as a New Model for the In Vivo Study of Shigella flexneri Interaction with Phagocytes and Bacterial Autophagy |
title | The Zebrafish as a New Model for the In Vivo Study of Shigella flexneri Interaction with Phagocytes and Bacterial Autophagy |
title_full | The Zebrafish as a New Model for the In Vivo Study of Shigella flexneri Interaction with Phagocytes and Bacterial Autophagy |
title_fullStr | The Zebrafish as a New Model for the In Vivo Study of Shigella flexneri Interaction with Phagocytes and Bacterial Autophagy |
title_full_unstemmed | The Zebrafish as a New Model for the In Vivo Study of Shigella flexneri Interaction with Phagocytes and Bacterial Autophagy |
title_short | The Zebrafish as a New Model for the In Vivo Study of Shigella flexneri Interaction with Phagocytes and Bacterial Autophagy |
title_sort | zebrafish as a new model for the in vivo study of shigella flexneri interaction with phagocytes and bacterial autophagy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764221/ https://www.ncbi.nlm.nih.gov/pubmed/24039575 http://dx.doi.org/10.1371/journal.ppat.1003588 |
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