The Zebrafish as a New Model for the In Vivo Study of Shigella flexneri Interaction with Phagocytes and Bacterial Autophagy
2013
Mostowy, Serge | Boucontet, Laurent | Moya, Maria J. Mazon | Sirianni, Andrea | Boudinot, Pierre | Hollinshead, Michael | Cossart, Pascale | Herbomel, Philippe | Levraud, Jean-Pierre | Colucci-Guyon, Emma | Interactions Bactéries-Cellules (UIBC) ; Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Medical Research Council Centre for Molecular Bacteriology and Infection [Londres, Royaume-Uni] (MRC CMBI) ; Imperial College London | Macrophages et Développement de l'Immunité ; Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) | Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)) ; Institut National de la Recherche Agronomique (INRA) | Imperial College London | Programmes Transversaux de Recherche (PTR) grant from Institut Pasteur [372]; Zebraflam grant from Agence Nationale de Recherche [ANR-10-MIDI-009] | ANR-10-MIDI-0009,ZebraFlam,Signaux et cellules de la réponse inflammatoire: suivi en temps réel chez un vertébré entier, le danio zébré(2010)
International audience
اظهر المزيد [+] اقل [-]إنجليزي. 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.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل Institut national de la recherche agronomique