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L'infection MURINE PAR Schistosoma Bovis N° d'ordre: UNIVERSITE DES SCIENCES ET TECHNOLOGIES DE LILLE I pour obtenir le grade de Docteur en Sciences de la Vie et de la Santé Discipline : IMMUNOLOGIE présentée et soutenue publiquement par L'INFECTION MURINE PAR Schistosoma bovis 1 - Analyse des Paramètres Parasitaires et Immunologiques II - Approche des Mécanismes Protecteurs Induits par la S. bovis 28 kDa Glutathion S-transférase Soutenue le 12 Février 1998 devant la commission d'examen: Directeur de thèse : Professeur A. Capron Président du Jury : Professeur G. SPIK Rapporteurs : Professeur J. VERCRUYSSE Professeur H. GRAS-MASSE Examinateurs : Professeur A. CAPRON Professeur M.TAYLOR Docteur C. VERWAERDE Docteur J.M.GRZYCH 2 Ce travail a été réalisé au centre d'Immunologie et de Biologie Parasitaire INSERM U167 Institut Pasteur de Lille sous la direction du Professeur A. Capron et plus particulièrement dans le groupe de recherche dirigé par le Docteur J.M. Grzych et en collaboration avec le Laboratorio de Parasitologia do Instituto Nacional de Saude Dr. Ricardo Jorge Porto - Portugal dirigé par le Professeur Maria de Lourdes Sampaio Silva Ce travail a été financé par la CEE (Fellowship - contrat ERBCHBICT 941496) 3 de dédie cette thèse à otfes parents.... cU'erci pdur Pdtre encdurag-ement et Pdtre sdutien, j'e Pdus pdrte dans mdn cdeur. 4 Qualquer musica, ah, qualquer, Logo que me tire da alma Esta incerteza que quer Qualquer impossivel calma! Qualquer musica - guitarra, Viola, harmonio, realejo ... Um canto que se desgarra ... Um sonho em que nada vejo ... Qualquer coisa que nao vida! Jota, fado, a confusao Da ultima dança vi vida ... Que eu nao sinta o coraçao! Estas so. Ninguém o sabe. Cala e finge. Mas finge sem fingimento. Nada esperes que em ti ja nao exista, Cada um consigo é triste. Tens sol se ha sol, ramos se ramos buscas, Sorte se a sorte é dada. Fernando Pessoa 5 A Monsieur le Professeur A. Capron, Vous m'avez chaleureusement accueillie dans votre unité. C'est avec votre permission et soutien que ce travail a pu aboutir. Que ce mémoire soit le témoignage de ma sincère reconnaissance et de mon profond respect. A Madame le Professeur G. Spik qui m'a fait l'honneur de présider cette thèse. A Madame le Professeur H. Gras-Masse et Monsieur le Professeur 1. Vercruysse qui ont accepté de juger ce travail. Je vous en suis très reconnaissante. A Madame le Docteur C. Verwaerde pour avoir accepté de porter un jugement sur ce travail, pour votre disponibilité, la qualité de vos suggestions scientifiques et vos précieuses critiques au cours de ces deux dernières années, je tiens à vous remercier chaleureusement. A Monsieur le Professeur G. Taylor pour l'honneur que vous me faites en participant à mon jury, soyez assuré de ma profonde reconnaissance. A Monsieur le Docteur ].M. Grzych pour m'avoir fait confiance tout au long de ce travail, je vous remercie. A Monsieur le Docteur R.]. Pierce pour votre coopération et votre participation dans la correction des articles et de ce manuscrit. A Madame le Professeur M. Capron pour votre disponibilité et votre enthousiasme. A Madame le Professeur Maria de Lourdes Sampaio Silva pour m'avoir accueillie au sein de son équipe et m'avoir permis de débuter le dur travail qu'est la recherche. 6 A mes chères ... Sophia, pour tes précieux enseignements, tes sages conseils et les "millions de cellules"! ... Josette, aux longues heures partagées, à tes inoubliables enseignements et au "petit bout... encore un petit bout d'intestin"! ... Que cette thèse soit le témoignage de mon amitié et sincère respect. A ma Sophie ... à notre heure de folie, à nos rires et à nos larmes. Merci ... d'avoir eu toujours le temps de m'écouter, de tes sincères conseils et de ton amitié. Merci encore de m'avoir fait "tatie portugaise" de ta belle Julie. Tu sais ... "C'est pas écrit dans les livres ... le temps c'est de l'Amour. ... " A ma Joaninha ... à nos longues soirées de bavardage!! ... aux notes musicales ... aux silences partagés ... aux astronautes complices ... "Je regarderai la nuit, une étoile me sourira ... " Thank you .... Karine ... à nos disputes dépassées... aux bons souvenirs de nos premiers pas en ski.... et le retour à Stoneage. A la blondinette Vinca ... un phénomène. Pascal...à nos murmures and hard-hot Wales nights. A Kader, le "pas assez beau et intelligent" Sénégalais que je connais. Bertrand .. .le plus grand « nain ch'ti » et tes drôles de blagues. A Estelle ... pour le baby-sitting du cactus. Rodolfo ... "Je crois bien que j'aurai besoin de te voir Quand tu danses, quand tu danses Sans te parler, ni déranger, mais te voir Quand tu danses, y songes-tu ? Quand tu danses, y songes-tu? Et toutes les peines, toutes, contre une seule de nos minutes ...... J.J.Goldman" Sylvain ... aux longues soirées de café portugais ... au cafard de "Michel Portal" ... et à nos explorations gabonaises ! ! Merci pour tous les bons moments .... d'amitié. 7 A Marina ... à qui je dédie une partie de ce mémoire et à nos loisirs communs. A Tobias ... Je n'oublierai jamais ta patience et ta gentillesse. Merci de votre amitié. A ceux qui sont déjà partis .... hablando ..... Hector et Esteban ... et le "du pipo" de G. Renom. A tous ceux qui "traînent" à la machine à café du CIBP. A Jean-Loup Neyrinck ... pour m'avoir « informatisée » et aux pensées communes. A Chantal Kizonzolo et Jean Marc pour leurs disponibilité et efficacité. A Florent.. .le plus rigolo des "Gaubert" ..... et à Gaëlle ... pour son délicieux Tiramisu. A mes compagnons du Portugal ...... Susana et sa famille, ..... Lurdinhas et Aninhas, Sr. Seixas, Zé-Manel, Filipa et tous ceux que je ne peux pas citer.. .... Merci de votre amitié. Et encore à ma famille ..... 8 Ce travail a fait l'objet des publications et communications suivantes Publications Viana da Costa A., Gaubert S., Fontaine J., Lafitte S., Seixas A., Sampaio Silva M.L., Capron A., Grzych J.M. 1997. "Murine Schistosoma bovis infection : analysis of parasitic and immune pararneters". Accepté dans Parasit. Immunol. Viana da Costa A., Gaubert S., Lafitte S., Fontaine J., Bossus M., Gra Masse H., Capron A., Grzych J.M., 1997. "Antibodies to Schistosoma bovis 28kDa Glutathione $-Transferase affect schistosome egg viability : relationship with GST activity" Soumis à J. Immunol. Viana da Costa A., Fontaine J., Lafitte S., Seixas A., Sampaio Silva M.L., Capron A., Grzych J.M., Verwaerde C., 1997."Resistance to reinfection with Schistosoma bovis in the mo use" En preparation. Communications *SFI-Société Française d'Immunologie, Marseille, France 25-27 November 1997. "Schistosoma bovis glutathion S-Transferase (rSb28GST): inhibition de la viabilité des oeufs." *SPP-Sociedade Portuguesa de Parasitologia (V Congrès Ibérique de Parasitologie), Evora, Portugal 6-10 October 1997. Deux présentations orales. "Infecçao mutina por Schistosoma bovis : analise dos parametros Parasitologicos e Imunologicos" et "Analise in vivo e in vitro das propriedades biologicas dos anticorpos monoclonais contra a S. bovis r28GST". *BSP-British Society of Parasitology -Spring Meeting Manchester UK, 8-10 April 1997. Présentation orale. "In vitro and in vivo analysis of biological properties of mutine monoclonal antibodies to Schistosoma bovis 28GST protective antigen". *Meeting Université Libre de Bruxelles-Lille, 9 Janvier 1997. *Meeting "Journée Jeunes Chercheurs"-Lille France, 18 November 1996. "Analyse des propriétés biologiques in vivo des anticorps monoclonaux anti-S. bovis 28 Glutathion-S­ Transférase". *Meeting Lille-Université Libre de Bruxelles, 30 May 1995." Approches des propriétés effectrices des lgA dans les schistosorniases". 9 * Instituto Nacional de Saude Dr. Ricardo Jorge-Porto Portugal, 30 June 1995 at the Meeting "Serninario sobre Schistosomiase". Présentation orale. Aux cours de ces années, j'ai également participé aux travaux suivants Gaubert S., Viana da Costa A., Maurage C.A., Santos Lima E.C., Fontaine J., Lafitte S., Minoprio P., Capron A., Grzych JM., 1997."X-linked immunodeficiency affects the outcome in Schistosoma mansoni in the murine model". Soumis à Int. Immunol. Gaubert S., Santos Lima E.C., Viana da Costa A., Lafitte S., Fontaine J., Minoprio P., Capron A., Grzych JM., 1997. "CD5 B cells in mucosal IgA response during S. mansoni murine infection". En préparation. Sampaio Silva M., Correia Costa J.; Viana da Costa A., Pires M.A., Lopes A., Castro A., Monjour L. 1996."Antigenic components of excretory-secretory products of adult Fasciola hepatica recognized in human infections". Am. J. Med. Hyg.,54(2), 146-148. Monteiro L., Silveira A., Sampaio Silva M.L., Correia J.M., Costa A.M., Carvalho M.T., Coelho J.M., and Coelho T. 1996. "Taeniase-Cisticercose por Taenia solium. Estudo epidemeologico piloto numa aldeia do Norte de Portugal". Rev. Portuguesa de Doenças Infectiosas Vo1.3/4 : 182-188. Correia da Costa J.M., Viana da Costa A., Monteiro L., Oliveira P., Sampaio Silva M.L. "Immunodiagnosis of Human Neurocysticercosis : evaluation of ELISA and Immunoblotting using a commmercial antigen preparation". Soumis. * 2ème Congrès de Maladies Infectieuses-Octobre 19 9 3 Porto "Diagnostico laboratorial da Cisticercose humana pela técnica enzimatica de ELISA e Hemaglutinaçao indirecta" * Abstracts présentés au Congrès ICASEP I-V alencia 1991. "Immunobiology of the infection by Schistosoma bovis in the Balb/C model: extrapolation of the immunodiagnosis of the human schistosorniasis" et "Excretory- Secretory products of Fasciola hepatica , utilization in the immunodiagnosis of fascioliasis" et "Immunodiagnosis of humain Neurocysticercosis". 10
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