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Interactions entre le virus Bluetongue et cellules dendritiques lymphatiques du mouton

Présentée par : Monsieur Behzad HEMATI Discipline : IMMUNOLOGIE VIROLOGIE

 

 

«Interactions entre le virus Bluetongue et cellules dendritiques lymphatiques du mouton »

 

Abstract :

 

Bluetongue virus (BTV), an orbivirus of the reoviridae family comprises 24 serotypes and is responsible for an insect transmitted hemorrhagic disease in ruminants that generates important economic losses all over the world. The severity of the BTV induced syndrome as well as the duration of viraemia greatly varies between BTV serotypes and hosts. The innate response to the virus could be involved in host sensitivity and has not been studied.

 

We investigated the first steps of BTV dissemination and type I IFN response in the afferent lymphatic in sheep, right after intra-cutaneous delivery of the virus. We showed that BTV initially migrates in the skin draining lymph mainly associated to conventional dendritic cells (cDC). Lymph cDC supported BTV RNA, protein and infectious virus production of several serotypes, independently of viral attenuation. BTV expression in cDC did not impair their survival but rather favored it. Interaction of BTV with cDC preparation resulted in an increased expression of CD80 and CD86 as well as an increase in IL12, IL1b and IL6 mRNA expression. Finally lymph cDC cultured with BTV triggered stimulation of specific CD4 and CD8 T cell proliferation as well as IFNg production. BTV thus utilizes cDC for its first lymph dissemination step in the host without altering their classical immune function of antigen presentation, reflecting an optimal adaptation of the virus to its first cell target.

 

Besides, we found that type I IFN is detectable in 2 peaks (24 hours and day 5 - 6) in afferent lymph in parallel to the viral dissemination. Only lymph plasmacytoid (pDC) and not cDC were producing type I IFN (IFNa) to BTV, independently on viral serotype, on viral replication and on endosomal acidification.

 

Collectively these finding suggest the hypothesis that BTV replication in cDC and/or cDC and pDC responses might be involved in inter-individual susceptibility to BTV.

 

Informations complémentaires

Stéphan ZIENTARA, Inspecteur en Chef de Santé publique Vétérinaire à l'Ecole Vétérinaire de Maison Alfort- Rapporteur

Yolande RICHARD-CLAUSSE, Directeur de recherche au Service d'Immunologie-Virologie CEA- Rapporteur

Gilles MEYER, Maitre de Conférences à l'Institut National de recherche Agronomique (INRA) - Examinateur

Jean-Luc VAYSSIERE, Professeur des Universités, à l'Université de Versailles Saint-Quentin-en-Yvelines - Examinateur

Isabelle SCHWARTZ-CORNIL, Directeur de Recherche, à l'Institut National de la Recherche Agronomique, Jouy-en-Josas - Directeur de thèse

Micheline LAGRANGERIE, Ingénieur de recherche à l'INSITUT PASTEUR  - Examinateur

Contact :
Direction de la Recherche des Etudes Doctorales et de la Valorisation (DREDVal) :