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...

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Autores principales: Serge Mostowy, Laurent Boucontet, Maria J Mazon Moya, Andrea Sirianni, Pierre Boudinot, Michael Hollinshead, Pascale Cossart, Philippe Herbomel, Jean-Pierre Levraud, Emma Colucci-Guyon
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:f2b25e2ba579463bad05187a7f4dab332021-11-18T06:07:41ZThe zebrafish as a new model for the in vivo study of Shigella flexneri interaction with phagocytes and bacterial autophagy.1553-73661553-737410.1371/journal.ppat.1003588https://doaj.org/article/f2b25e2ba579463bad05187a7f4dab332013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24039575/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Autophagy, 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.Serge MostowyLaurent BoucontetMaria J Mazon MoyaAndrea SirianniPierre BoudinotMichael HollinsheadPascale CossartPhilippe HerbomelJean-Pierre LevraudEmma Colucci-GuyonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 9, p e1003588 (2013)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Serge Mostowy
Laurent Boucontet
Maria J Mazon Moya
Andrea Sirianni
Pierre Boudinot
Michael Hollinshead
Pascale Cossart
Philippe Herbomel
Jean-Pierre Levraud
Emma Colucci-Guyon
The zebrafish as a new model for the in vivo study of Shigella flexneri interaction with phagocytes and bacterial autophagy.
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 article
author Serge Mostowy
Laurent Boucontet
Maria J Mazon Moya
Andrea Sirianni
Pierre Boudinot
Michael Hollinshead
Pascale Cossart
Philippe Herbomel
Jean-Pierre Levraud
Emma Colucci-Guyon
author_facet Serge Mostowy
Laurent Boucontet
Maria J Mazon Moya
Andrea Sirianni
Pierre Boudinot
Michael Hollinshead
Pascale Cossart
Philippe Herbomel
Jean-Pierre Levraud
Emma Colucci-Guyon
author_sort Serge Mostowy
title 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_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_sort zebrafish as a new model for the in vivo study of shigella flexneri interaction with phagocytes and bacterial autophagy.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/f2b25e2ba579463bad05187a7f4dab33
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