Rôle des éosinophiles dans la régulation des populations d'Haemonchus contortus chez le mouton

Getachew Terefe

Description

Niveau: Supérieur, Doctorat, Bac+8
N° d'ordre : ……….. THESE Présentée Pour obtenir LE TITRE DE DOCTEUR DE L'INSTITUT NATIONAL POLYTECHNIQUE DE TOULOUSE École doctorale : SCIENCES ECOLOGIQUES, VETERINAIRES, AGRONOMIQUES ET BIOINGENIERIES Spécialité : Qualité et Sécurité des Aliments Par M. Getachew TEREFE Titre de la thèse : Rôle des éosinophiles dans la régulation des populations d'Haemonchus contortus chez le mouton. Soutenue le 11 juin 2007 devant le jury composé de : Professeur Alain MILON Président Docteur Philippe JACQUIET Directeur de thèse Docteur Odile BAIN Rapporteur Professeur Allal DAKKAK Rapporteur Professeur Philippe DORCHIES Membre Professeur Jimmy DUNCAN Membre Professeur Jean-François MAGNAVAL Membre Docteur Isabelle OSWALD Membre

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• jury members while


• interaction hôtes-agentes pathogènes


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• research station


• professeur jimmy

Sujets

• Lacoste
• Institut national polytechnique de Toulouse
• Traoré
• Prévôt
• Duncan

Informations

• Publié par: profil-zyak-2012
• Publié le: 01 juin 2007
• Nombre de lectures: 26
• Langue: English
• Poids de l'ouvrage: 3 Mo

Extrait

N° d’ordre : ………..




THESE

Présentée
Pour obtenir

LE TITRE DE DOCTEUR DE L’INSTITUT NATIONAL POLYTECHNIQUE DE TOULOUSE

École doctorale : SCIENCES ECOLOGIQUES, VETERINAIRES, AGRONOMIQUES ET BIOINGENIERIES

Spécialité : Qualité et Sécurité des Aliments

Par M. Getachew TEREFE

Titre de la thèse : Rôle des éosinophiles dans la régulation des populations d’Haemonchus
contortus chez le mouton.


Soutenue le 11 juin 2007 devant le jury composé de :

Professeur Alain MILON Président
Docteur Philippe JACQUIET Directeur de thèse
Docteur Odile BAIN Rapporteur
Professeur Allal DAKKAK
Professeur Philippe DORCHIES Membre
Professeur Jimmy DUNCAN Membre
Professeur Jean-François MAGNAVAL Membre
Docteur Isabelle OSWALD Membre

ACKNOWLEDGMENTS


At the outset, I would like to express my appreciation to Dr. Philippe JACQUIET for his
advice during my doctoral research endeavour for the past three years. As my supervisor, his
observations and comments helped me to establish the overall direction of the research and to
move forward with investigation in depth. I benefited immensely from our discussions and
from the enormous encouragements he extended to me.

I also like to express my deepest gratitude to Professor Philippe DORCHIES for his help
in securing the French Government Scholarship and for organizing a very interesting
scientific environment. Moreover, I appreciated the many discussions I had with him in which
he was full of ideas and his encouragement and advice that motivated me to work hard.

I am greatly indebted to Dr. Christelle GRISEZ, François PREVOT, Jean-Paul
BERGAUD, Drs. Caroline LACROUX and Gilles FOUCRAS for excellent technical
assistance and for our pleasant collaboration.

It is a great pleasure to thank the President of the jury (also Director of Ecole National
Vétérinaire de Toulouse), Prof. Alain MILON, the Rapporteurs, Prof. Allal DAKKAK and
Dr. Odile BAIN and the jury members, Dr. Isabelle OSWALD, Profs. Philippe DORCHIES,
Jimmy DUNCAN and Jean-François MAGNAVAL for their kind willingness to referee this
thesis and to take part in the examination committee. Profs. Ph. DORCHIES and J. DUNCAN
were members of the external examiners board when I publicly defended my DVM thesis at
Debre Zeit (Ethiopia) in 1993. I am happy to see them again as jury members while I defend
my Doctoral thesis.

I would like to thank the Embassy of France in Ethiopia for providing me with the French
Government Scholarship (Bourse du Gouvernement Français), and CROUS-Toulouse for
facilitating my stay in France.

1 Thanks are also due to members of the thesis committee: Dr. G. FOUCRAS, Dr. I.
OSWALD and Prof. Ph. DORCHIES for forwarding valuable comments and suggestions that
enabled us to refine our experimental approaches.

My heartfelt acknowledgement also goes to the INRA research station (domaine INRA de
la Sapinière (Cher)) for providing us with most of the experimental animals that have been
used throughout our studies, and the Director of the INRA research unit (UMR 1225,
Interaction hôtes-agentes pathogènes), F. SCHELCHER, for allowing me to work with the
UMR research team.

I thank MC. FLUMIAN and C. BLEURT from the Department of Anatomy and
Pathology for their help with histological preparations, and M. SARDA, C.
FABREGUETTES, JM. DELMAS, C. BERNAD, C. ESPIE (ENVT) and M. LACOSTE
(INP-Toulouse), who have been kind enough to help in their respective roles.

I am grateful to my colleagues, Cuong K. NGUYEN and Ibrahima TRAORE for their
collaboration, useful advice and for making life fun while working.

I would like to express my sincere thanks to Dr. Kelay BELIHU from Debre Zeit for
proof reading some of the chapters and for his valuable comments and suggestions.

Words cannot express the contribution of the Ethiopian diaspora in and around Toulouse:
Samuel(s), Zenebech, Meraf, Silvia, Addis, Samrawit, Dejene, Efrem, Tadesse, Worku,
Genet, Azeb, Mesfin, Getu, Mengistu, Sara, just to mention a few. Let me say
“Ameseginalehu” ( ), an Amharic term to say thank you, to dear friends for
inspiring me during the last few years, for creating adventures, for supporting me when times
were rough and for making me feel at home throughout my stay.


Getachew Terefe
June 2007, Toulouse (France)

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3Table of contents page

Acknowledgement ------------------------------------------------------------------------------ 1
Dedication--------------------------------------------------------------------------------------- 3
Introduction ------------------------------------------------------------------------------------- 6
Part I. Literature review --------------------------------------------------------------------- 12
1. Haemonchus contortus ------------------------------------------------------------- 13
1.1. Morphology ---------------------------------------------------------------- 13
1.2. Life cycle ------------------------------------------------------------------- 14
1.3. Epidemiology -------------------------------------------------------------- 16
1.4. Clinical manifestations and diagnostic methods----------------------- 19
1.5. Pathophysiology of abomasal parasitism------------------------------- 20
1.6. Control of haemonchosis ------------------------------------------------- 25
2. Immune response and GI parasitism---------------------------------------------- 35
2.1. Innate immunity ----------------------------------------------------------- 35
2.2. Adaptive immunity -------------------------------------------------------- 36
2.3. Th2-polarized response during GI parasitic infections --------------- 40
2.4. Role of effector cells & antibody --------------------------------------- 43
3. Eosinophils--------------------------------------------------------------------------- 49
3.1. Biology---------------------------------------------------------------------- 49
3.2. Eosinophils in allergy ----------------------------------------------------- 57
3.3. Role of eosinophils in GI parasitism ------------------------------------ 59
Part II. Materials and methods-------------------------------------------------------------- 64
1. Experimental animals--------------------------------------------------------------- 65
1.1. The INRA 401 breed ------------------------------------------------------ 65
1.2. The Barbados Black Belly breed ---------------------------------------- 66
1.3. The Tarasconnais breed--------------------------------------------------- 66
2. The parasite and experimental infections 67
3. Methods ------------------------------------------------------------------------------ 67
3.1. Parasitological parameters------------------------------------------------ 67
3.2. Immunological parameters ----------------------------------------------- 69
43.3. Blood eosinophil isolation and in vitro tests --------------------------- 76
3.4. Intra-abomasal infection -------------------------------------------------- 80
3.5. Ultrastructural studies----------------------------------------------------- 80
3.6. Biochemical tests ---------------------------------------------------------- 81
Part III. Results ------------------------------------------------------------------------------- 84
1. Demonstration of the larval killing ability of sheep eosinophils in vitro----- 85
Publication No. 1 -------------------------------------------------- 87
2. Effect of artificially enhancing or reducing blood eosinophilic responses on
the life traits of H. contortus in sheep -------------------------------------------- 95
2.1. Enhancing host’s eosinophilic response to H. contortus by
co-infection with O. ovis.-------------------------------------------------- 95
Publication No. 2 -------------------------------------------------- 97
2.2. Suppressing the inflammatory responses in a resistant breed
(Barbados Black Belly) using sodium cromoglycate during
H. contortus infection----------------------------------------------------- 110
Publication No. 3 (in press)-------------------------------------- 111
3. Factors influencing resistance to H. contortus infection with special
reference to eosinophilia in sheep------------------------------------------------ 123
3.1. Animal breed as a factor of variation ---------------------------------- 123
Publication No. 4 (in press)-------------------------------------- 125
Publication No.5 (in preparation)------------------------------- 135
3.2. Animal age as a factor of variation------------------------------------- 154
Part IV. General discussion and perspective--------------------------------------------- 160
1. Rationale ------------------------------------------