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The AATTOL project aims at characterizing the molecular bases of tolerance to a major parasitic disease in livestock, the trypanosomosis. African animal trypanosomosis (AAT), a vector-borne disease caused by blood protozoan parasites of the genus Trypanosoma, is a major constraint to the development of cattle breeding in the humid and sub-humid zones of Africa through the high morbidity and mortality it causes. Currently, control measures based on vector control or the use of trypanocide drugs are not satisfactory and no vaccine is available. However, some taurine breeds in West Africa have the capacity to tolerate the disease: they control the proliferation of the trypanosomes and the associated-pathogenic effects, contrary to the indicine and European taurine breeds who usually die of the infection in the absence treatment. This ability, called trypanotolerance, has probably evolved as a result of selection pressure exerted by parasites on cattle populations who first colonized the endemic areas of the disease. The exploitation of the part of the host genetic variability associated to the tolerance to the disease, through the husbandry of both tolerant and productive animals, could allow controlling AAT, while decreasing the cost of the fight, its negative effects on the environment and the spread of the parasite. In addition, the characterization of the molecular bases of an effective immunity, the precise knowledge of the pathophysiology of the infection, of host-pathogen interactions and the identification of genes and physiological pathways of the host involved in trypanotolerance would allow the establishment of effective control methods based on the discovery and the use of new therapeutic molecules or the introduction of an innovative vaccine strategy targeting keys molecules of the parasite. The objectives of this project are thus to identify the molecular bases of tolerance to trypanosomosis caused by Trypanosoma congolense in West African cattle and to improve knowledge on the host-parasite interactions. We propose to jointly study the transcriptomes of the host and parasite in the blood compartment during an experimental infection of 5 West African cattle breeds. The technique we have chosen is the Digital Gene Expression, based on the use of high throughput sequencing. The specific objectives are: 1) to characterize the trypanotolerant phenotype during the experimental infection of cattle from five different breeds: the taurine trypanotolerant N'Dama breed, well described in the literature, the Fulani Zebu, a well-known indicine trypanosusceptible breed, the Baoulé and the Lagunaire, two taurine trypanotolerant breeds very little studied so far, and the Borgou, a mixed breed between the Baoulé and the Fulani Zebu, which could represent a breed with a great potential for genetic improvement to associate trypanotolerance and productivity in the future ; 2) to study the genes expression levels of the parasite and the host blood cells during an experimental infection, in order to identify genes, genes networks and biological pathways involved in trypanotolerance, to propose virulence factors of the parasite and to obtain an overview of the dialogue between the host cells and the parasite; 3) and finally to propose candidate genes potentially responsible for trypanotolerance by combining data from this work with genetic data we have, through our own works and the literature.
The AATTOL project aims at characterizing the molecular bases of tolerance to a major parasitic disease in livestock, the trypanosomosis. African animal trypanosomosis (AAT), a vector-borne disease caused by blood protozoan parasites of the genus Trypanosoma, is a major constraint to the development of cattle breeding in the humid and sub-humid zones of Africa through the high morbidity and mortality it causes. Currently, control measures based on vector control or the use of trypanocide drugs are not satisfactory and no vaccine is available. However, some taurine breeds in West Africa have the capacity to tolerate the disease: they control the proliferation of the trypanosomes and the associated-pathogenic effects, contrary to the indicine and European taurine breeds who usually die of the infection in the absence treatment. This ability, called trypanotolerance, has probably evolved as a result of selection pressure exerted by parasites on cattle populations who first colonized the endemic areas of the disease. The exploitation of the part of the host genetic variability associated to the tolerance to the disease, through the husbandry of both tolerant and productive animals, could allow controlling AAT, while decreasing the cost of the fight, its negative effects on the environment and the spread of the parasite. In addition, the characterization of the molecular bases of an effective immunity, the precise knowledge of the pathophysiology of the infection, of host-pathogen interactions and the identification of genes and physiological pathways of the host involved in trypanotolerance would allow the establishment of effective control methods based on the discovery and the use of new therapeutic molecules or the introduction of an innovative vaccine strategy targeting keys molecules of the parasite. The objectives of this project are thus to identify the molecular bases of tolerance to trypanosomosis caused by Trypanosoma congolense in West African cattle and to improve knowledge on the host-parasite interactions. We propose to jointly study the transcriptomes of the host and parasite in the blood compartment during an experimental infection of 5 West African cattle breeds. The technique we have chosen is the Digital Gene Expression, based on the use of high throughput sequencing. The specific objectives are: 1) to characterize the trypanotolerant phenotype during the experimental infection of cattle from five different breeds: the taurine trypanotolerant N'Dama breed, well described in the literature, the Fulani Zebu, a well-known indicine trypanosusceptible breed, the Baoulé and the Lagunaire, two taurine trypanotolerant breeds very little studied so far, and the Borgou, a mixed breed between the Baoulé and the Fulani Zebu, which could represent a breed with a great potential for genetic improvement to associate trypanotolerance and productivity in the future ; 2) to study the genes expression levels of the parasite and the host blood cells during an experimental infection, in order to identify genes, genes networks and biological pathways involved in trypanotolerance, to propose virulence factors of the parasite and to obtain an overview of the dialogue between the host cells and the parasite; 3) and finally to propose candidate genes potentially responsible for trypanotolerance by combining data from this work with genetic data we have, through our own works and the literature.
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