 |
Assistant Professor(BSc, PhD Univ. Lille I)Tel.: (514)398-7722 |
Research Interests
Publications
Interactions between the intracellular protozoan parasite Toxoplasma gondii and the host cell antigen presentation pathways
Studies in the lab focus on host-pathogen interactions during infection by the parasite Toxoplasma gondii. T. gondii, like other species of the phylum Apicomplexa (Plasmodium sp., Cryptosporidium sp., and thousands of other parasite species), is a major pathogen of humans and animals. Clinical symptoms of toxoplasmosis are generally benign in immune competent individuals, but this food and water-borne parasite causes serious diseases when transmitted to the developing fetus, and in immune compromised individuals (transplant, cancer, AIDS patients).
The lack of strong clinical symptoms and the chronic nature of the disease in immune competent individuals are due to the robust T cell response, which is elicited during the acute phase of a T. gondii infection, and which is long lasting and protective against the parasite. This indicates that, while T. gondii can clearly manipulate several aspects of the host immune response, presentation of T. gondii antigens nevertheless does occur, according to mechanisms that are largely undefined. Apicomplexans are unicellular eukaryotic organisms, which grow and divide in a vacuole that is established within the cells of infected hosts (in the case of T. gondii, the range of permissive host cells extends to include any nucleated cells from any warm-blooded vertebrates). This vacuole is a non-degradative compartment and is not part of the host cell endocytic and secretory pathways required for the presentation of endogenous antigens in the context of MHC molecules. This raises a number of questions, including: how are T. gondii antigens presented? By what types of cells?
Of the apicomplexan parasites, T. gondii is by far the most amenable to genetic manipulation and analysis. It is possible to combine approaches of molecular immunology, genomics, genetics and cell and molecular biology to study the effects of either acute or chronic T. gondii infection in host cells and on host immune effectors. Since the complexity of the parasite lifestyle and the lack of known T. gondii T cell-restricted epitopes have impaired our ability to follow clonal T cell responses and antigen presentation, we have therefore developed a series of transgenic parasites expressing model antigens. These parasites, combined with other reagents, allow not only the study of molecular aspects of antigen presentation via MHC-I and MHC-II and suppression of dendritic cell maturation in cells actively infected by T. gondii, but also the design of novel genetic screens to isolate parasite molecules that interact with the host cell and the host immune response.