Assistant Professor
Tel.: (514)398-7722
Fax: (514)398-7857
florence [dot] dzierszinski [at] mcgill [dot] ca (Email)
Research Interests
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.
Selected Publications
- John B, Harris TH, Tait ED, Wilson EH, Gregg B, Ng LG, Mrass P, Roos DS, Dzierszinski F, Weninger W, Hunter CA. (2009)
- Dynamic Imaging of CD8(+) T cells and dendritic cells during infection with Toxoplasma gondii. PLoS Pathog. 5(7):e1000505.
- Jordan KA, Wilson EH, Tait ED, Fox BA, Roos DS, Bzik DJ, Dzierszinski F, Hunter CA. (2009)
- Kinetics and phenotype of vaccine-induced CD8+ T-cell responses to Toxoplasma gondii. Infect Immun. 77(9):3894-901.
- Pepper M, Dzierszinski F, Wilson E, Tait E, Fang Q, Yarovinsky F, Laufer TM, Roos D, Hunter CA. (2008)
- Plasmacytoid dendritic cells are activated by Toxoplasma gondii to present antigen and produce cytokines. J Immunol. 180(9):6229-36.
- Dzierszinski FS, Hunter CA. (2008)
- Advances in the use of genetically engineered parasites to study immunity to Toxoplasma gondii. Parasite Immunol. 30(4):235-44.
- Menard LC, Minns LA, Darche S, Mielcarz DW, Foureau DM, Roos D, Dzierszinski F, Kasper LH, Buzoni-Gatel D. (2007)
- B cells amplify IFN-gamma production by T cells via a TNF-alpha-mediated mechanism. J Immunol. 179(7):4857-66.
- Dzierszinski F, Pepper M, Stumhofer JS, LaRosa DF, Wilson EH, Turka LA, Halonen SK, Hunter CA, Roos DS. (2007)
- Presentation of Toxoplasma gondii antigens via the endogenous major histocompatibility complex class I pathway in nonprofessional and professional antigen-presenting cells. Infect Immun. 75(11):5200-9.
- Dzierszinski, Florence; Knoll, L.J. (2007)
- Biology of bradyzoites, In Toxoplasma: Cell and Molecular Biology, chap. 17, Eds. D. Soldati, J. Ajioka.
- Wilson EH, Wille-Reece U, Dzierszinski F, Hunter CA. (2005)
- A critical role for IL-10 in limiting inflammation during toxoplasmic encephalitis. J Neuroimmunol. 165: 63-74.
- Pepper M*, Dzierszinski F*, Crawford A, Hunter CA, Roos DS. (2004)
- Development of a system to study CD4+-T-cell responses to transgenic ovalbumin-expressing Toxoplasma gondii during toxoplasmosis. Infect Immun. 72: 7240-7246. * Co-1st authors
- Dzierszinski F, Nishi M, Ouko L, Roos DS. (2004)
- Dynamics of Toxoplasma gondii differentiation. Eukaryot Cell. 3: 992-1003.
- McKee AS*, Dzierszinski F*, Boes M, Roos DS, Pearce EJ. (2004)
- Functional inactivation of immature dendritic cells by the intracellular parasite Toxoplasma gondii. J Immunol. 173: 2632-2640. * Co-1st authors
- Cervi L, MacDonald AS, Kane C, Dzierszinski F, Pearce EJ. (2004)
- Cutting edge: dendritic cells copulsed with microbial and helminth antigens undergo modified maturation, segregate the antigens to distinct intracellular compartments, and concurrently induce microbe-specific Th1 and helminth-specific Th2 responses. J Immunol. 172: 2016-2020.
- Coppin A, Dzierszinski F, Legrand S, Mortuaire M, Ferguson D, Tomavo S. (2003)
- Developmentally regulated biosynthesis of carbohydrate and storage polysaccharide during differentiation and tissue cyst formation in Toxoplasma gondii. Biochimie. 85: 353-361.
- Dzierszinski F, Coppin A, Mortuaire M, Dewailly E, Slomianny C, Ameisen JC, DeBels F, Tomavo, S. (2002)
- Ligands of the peripheral benzodiazepine receptor are potent inhibitors of Plasmodium falciparum and Toxoplasma gondii in vitro. Antimicrob Agents Chemother. 46: 3197-3207.