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Host Response and Bacterial Virulence During Acute and Persistent Burkholderia Cepacia Complex Infection Using Zebrafish Embryos Jennifer Mesureur

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Host Response and Bacterial Virulence During Acute and Persistent Burkholderia Cepacia Complex Infection Using Zebrafish Embryos Jennifer Mesureur Host response and bacterial virulence during acute and persistent Burkholderia cepacia complex infection using zebrafish embryos Jennifer Mesureur To cite this version: Jennifer Mesureur. Host response and bacterial virulence during acute and persistent Burkholderia cepacia complex infection using zebrafish embryos. Animal biology. Université Montpellier, 2015. English. NNT : 2015MONTT024. tel-02936456 HAL Id: tel-02936456 https://tel.archives-ouvertes.fr/tel-02936456 Submitted on 11 Sep 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Délivré par l’Université Montpellier Préparée au sein de l’école doctorale Sciences Chimiques et Biologiques pour la Santé (ED168) Et de l’unité de recherche INSERM U1047 Spécialité : Microbiologie, Interaction hôte- pathogène Présentée par Jennifer MESUREUR Réponse de l’h ôte et virulence bactérienne durant une infection aiguë ou persistante causée par le complexe Burkholderia cepacia chez l’embryon de poisson -zèbre (Danio rerio ) Soutenue à Nîmes, le 24 juillet 2015 devant le jury composé de Mr Georges LUTFALLA , DR, CNRS DIMNP, Montpellier Président du Jury Mr Miguel VALVANO , Pr, Queen’s University Belfast Rapporteur Mr Jean-Pierre LEVRAUD , DR, Institut Pasteur Paris Rapporteur Mr Jean-Jacques LETESSON , Pr, University of Namur Examinateur Mme Annette VERGUNST , CR1, INSERM U1047, Nîmes Directeur de thèse 1 2 3 4 REMERCIEMENTS C’est l’heure des remerciements , ce qui sous-entend bientôt les au-revoir et les adieux à un certain nombre de personnes. Je tien s tout d’abord à remercier très vivement Annette. Ces quatre dernières années ont été très intenses et instructives pour moi. Tu m’as appris tellement de choses à la fois scientifiquement et sur ma propre personnalité et mon comportement. J’espère m’être un peu améliorée depuis. Merci de m’avoir accordé ta confiance et la liberté dont j’avais besoin pour m’épanouir. Tu as été comme une deuxième maman pendant tout ce temps, toujours là pour m’aider et me soutenir quand le moral n’était pas au beau fixe. Cette expérience restera à jamais gravée dans mon esprit et mon cœur , surtout après ce mois de mai très intense. J’espère juste une chose : être à la hauteur des espoirs qui tu as placés en moi et, pourquoi pas, revenir un jour pour travailler à nouveau ensemble. Merci à David, tout d’abord , pour m’avoir accueillie au sein de ton équipe et pour ton aide pour améliorer mon anglais avec Annette, car ce n’était pas gagné au début. Et aussi pour toutes les conversations gastronomiques lors des repas le midi. Merci à Jean-Jacques Letesson et Georges Lutfalla pour m’avoir suivie tout au long de ma thèse lors de mes trois comités de thèse et prodigué vos conseils. Et Georges, merci pour votre lignée mpeg1 qui a été très importante pour mes travaux de thèse. Et je tiens à vous remercier de faire partie de mon jury final. Merci beaucoup à Jean-Pierre Levraud et Miguel Valvano d’avoir accepté d’être les rapporteurs de ma thèse et de participer à ma soutenance de thèse. Merci à vous pour le temps que vous avez passé à lire ma thèse et pour vos conseils et suggestions. Merci à l’Université de Montpellier et l’école doctorale CBS2 sans qui je n’aurai pas pu faire cette thèse. Merci à Jean-Philippe et au CHU de Nîmes pour m’av oir permis de continuer et finir ma thèse. 5 Je tiens aussi à remercier Annemarie Meijer et son équipe pour son accueil lors de mes séjours à Leiden et tous leurs conseils tout au long de mes travaux. Merci aussi Amke et Hans pour votre accueil chaleureux lors de mon dernier voyage à Leiden , c’était vraiment merveilleux. Maintenant place à tous mes collègues du laboratoire. D’abord ceux qui sont partis : merci Gisou pour tes reliques qui m’ont bien fait rire ; Joana et Sébastien pour votre travail et votre aide ; Bashir, Nourreddine et Nabil pour vos délires et toutes nos soirées avec Christine et notamment mes 25 ans ; et Cyril, mon super stagiaire, qui a vraiment bien bossé et m’a beaucoup aidée. Maintenant ceux qui sont encore là. Merci à la « team clinique », Jean-Philippe, Catherine et Alix pour toutes nos conversations scientifiques et parfois moins, j’ai beaucoup appris en bactério avec vous. Merci à la « team Brucella » où je me suis greffée ces six derniers mois. Merci Anne pour m’avoir supportée et aidée sur le projet mass spec ; et pour tes conseils, ton franc parler et ton humour. Merci Christine, grâce à toi, maintenant je mange des légumes et j’ai même fait un marathon en équipe, qui l’aurait cru ! Merci à Karellen et Philippe. Et enfin la « team zebrafish » avec Lili et Margarida pour toutes nos conversations et tout ce que nous avons fait ensemble. Et bien sûr je n’oublie pas Fathia , pour tout le travail qu’elle fait au quotidien et qui nous simplifie grandement la vie et Christine pour ton aide administrative, ton écoute et toutes nos autres conversations. Merci aussi à Marc car grâce à lui, on va pouvoir fêter dignement cette soutenance. Et le plus important pour la fin, ma famille, mes amis, mon chéri d’amour et bien sûr mes animaux. Merci à mes parents et mes frères qui m’ont toujours soutenue et permis de poursuivre mes études et ma passion, l’équitation, durant toutes ces années. Je vous aime. Merci Gabriel, tu étais mon élève et maintenant un super pote de rugby et de beuverie. On s’est bi en amusés depuis un an et j’ai bien aimé toutes nos sorties et la féria qui restera mémorable pour moi. 6 Merci à mon Diddy Gaetan, mon meilleur ami. Merci pour ton soutien, ton écoute et tous tes bons conseils, heureusement que tu es là. Je t’adore. Un grand merci à Jérémy. Dommage que tu sois arrivé si tard, tes blagues pourries vont me manquer. Mais surtout heureusement que tu étais là pour me remonter le moral et m’aider quand ça n’allait pas. Notre amitié s’est vite formée et j’espère qu’elle va durer e ncore très longtemps et qu’on va continuer nos soirées jeux pour que je puisse tuer Ned et te botter le cul avec mes Elfes. Enfin, à toi mon Boubou, mon amour, tu es mon univers avec Fanda et Mystic (Bb pour les intimes) qui ont été d’un grand réconfort en ton absence. Nous sommes enfin à nouveau ensemble et pour longtemps. Merci pour ton soutien, ton aide et tout ce que tu fais au quotidien pour moi. Une nouvelle aventure se profile et il me tarde de la commencer avec toi. Je t’aime. 7 8 TABLE OF CONTENT ACRONYMS .................................................................................................... 11 ABSTRACT ...................................................................................................... 15 CHAPTER 1 – INTRODUCTION : HOST IMMUNE RESPONSE DURING BURKHOLDERIA CENOCEPACIA INFECTION ..................................................... 19 Part I. The human innate immune response .................................................................. 22 1.1. General information ............................................................................................................... 22 1.2. The innate immune response................................................................................................. 23 1.2.1. The role of neutrophils ................................................................................................... 25 1.2.2. The role of macrophages ................................................................................................ 27 1.2.3. The Toll-like receptor pathway and the inflammatory response ................................... 32 1.2.4. The complement system ................................................................................................ 37 1.2.5. Avoidance of host immune response by bacterial pathogen ......................................... 38 1.2.5.1. How not to be recognized by TLRs ................................................................. 40 1.2.5.2. Immunosuppressive actions ........................................................................... 40 1.2.5.3. Avoidance of phagocytic killing ...................................................................... 41 1.2.5.4. Escape from the autophagy pathway ............................................................. 43 1.2.5.5. Specific mechanisms against neutrophil killing .............................................. 44 1.2.6. The innate immune response of Cystic fibrosis and chronic granulomatous disease patients ..................................................................................................................................... 44 Part II. The zebrafish embryo model ............................................................................. 46 2.1. General description ................................................................................................................ 46 2.2. Vertebrate model to study bacterial, viral, fungal and parasitic infections ........................... 48 2.3. The zebrafish innate immune response ................................................................................. 49 2.3.1. Zebrafish haematopoiesis and macrophage activity .....................................................
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