HAL will be down for maintenance from Friday, June 10 at 4pm through Monday, June 13 at 9am. More information
Skip to Main content Skip to Navigation
Journal articles

The Zebrafish as a New Model for the In Vivo Study of Shigella flexneri Interaction with Phagocytes and Bacterial Autophagy

Abstract : 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.
Document type :
Journal articles
Complete list of metadata

Cited literature [66 references]  Display  Hide  Download

https://hal.inrae.fr/hal-02650798
Contributor : Migration Prodinra Connect in order to contact the contributor
Submitted on : Friday, May 29, 2020 - 2:52:38 PM
Last modification on : Thursday, April 7, 2022 - 10:10:27 AM

File

2013_Mostowy_Plos Path_1.pdf
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

Serge Mostowy, Laurent Boucontet, Maria J. Mazon Moya, Andrea Sirianni, Pierre Boudinot, et al.. The Zebrafish as a New Model for the In Vivo Study of Shigella flexneri Interaction with Phagocytes and Bacterial Autophagy. PLoS Pathogens, Public Library of Science, 2013, 9 (9), pp.e1003588. ⟨10.1371/journal.ppat.1003588⟩. ⟨hal-02650798⟩

Share

Metrics

Record views

12

Files downloads

7