Mary Stevenson

Professor

Centre for the Study of Host Resistance

Montreal General Hospital,
1650 Cedar Avenue
Montreal, Quebec H3G 1A4

Tel.: 514-934-1934 Ext. 44507
Fax: 514-934-8332
mary [dot] stevenson [at] mcgill [dot] ca (Email)

Research Interests

Together with HIV/AIDS and tuberculosis, malaria is a major infectious disease. Two thirds of the global population is at risk for malaria with sub-Saharan Africa accounting for about 90% of the deaths. Morbidity due to severe complications of this disease is extremely high among young children and pregnant women in this area. There is currently no vaccine available and drugs and insecticides are losing their effectiveness as the parasite and mosquito vectors, respectively, develop resistance to these tools of control. The major focus of the work in my laboratory is elucidation of the mechanisms of protective immunity against blood-stage malaria. One of our aims is to identify the cells and cytokines responsible for initiating innate immunity and inducing adaptive immunity to intraerythrocytic Plasmodium parasites, the causative agents of malaria. For our studies, we use a murine model of malaria in resistant and susceptible inbred mice infected with the rodent parasite, P. chabaudi AS. This rodent parasite is considered to have many similarities to the major human malaria parasite P. falciparum. We have identified that dendritic cells, NK cells, macrophages, and CD4+ T helper cells play important roles in the cell-mediated and antibody-dependent innate and adaptive immune responses required to control blood parasitemia and to clear and resolve the infection. We have also identified that a network of cytokines, involving IFN-gama, IL-12, TNF-alpha and GM-CSF, is critical for the development of protective immunity. Since anemia is a major cause of morbidity and mortality in children and pregnant women with severe malaria in sub-Saharan Africa, we are also examining cytokine regulation of erythropoiesis using in vivo and in vitro approaches. In collaboration with Dr. Philippe Gros, we are also identifying the major genes and their functions involved in susceptibility to malaria using the approaches of whole genome scanning, positional cloning and the candidate gene approach as well as transcriptional profiling of target tissues using cDNA microarrays and identification of important cell phenotypes by flow cytometry. Information obtained from our studies is important for the development of an efficacious vaccine strategy against blood-stage P. falciparum infection.

Selected Publications

Segura M, Su Z, Piccirillo C, Stevenson MM. (2007)

Impairment of dendritic cell function by excretory-secretory products: A potential mechanism for nematode-induced immunosuppression. Eur J Immunol.37: 1887-1904

Min-Oo G, Stevenson MM, Fortin A, Gros P. (2007)

Genetic control of host-pathogen interactions in mice. Novartis Found Symp. 281: 156-65; discussion 165-8, 208-9.

Fortin A, Pitari G, Tam M, Stevenson MM, Gros P. (2007)

Complex genetic control of susceptibility to malaria: positional cloning of the Char9 locus. J Exp Med. 204: 511-24.

Thawani N, Tam M, Chang KH, Stevenson MM. (2006)

Interferon-gamma mediates suppression of erythropoiesis but not reduced red cell survival following CpG-ODN administration in vivo. Exp Hematol. 34: 1451-61.

Roy, M.-F., Larivière, L., Wilkinson, R., Tam, M., Stevenson, M.M. and Malo, D. (2006)

Incremental expression of Tlr4 correlates with mouse resistance to Salmonella Typhimurium infection correlates with improved control of bacterial growth and increased expression of relevant genes. Genes Immun., 2006 Jun 1; [Epub ahead of print] .

Caron, J., Larivière, Tam, M., Stevenson, M.M., McKerly, C., Gros, P. and Malo, P. (2006)

The influence of Slc11a1 on the outcome of chronic Salmonella Enterititis infection in mice through Th polarization. Infect. Immun., 74: 2787-802. .

Su, Z., Segura, M. and Stevenson, M.M. (2006)

Reduced protective efficacy of blood-stage malaria vaccine by concurrent nematode infection. Infect. Immun. 74: 2138-44.

Ing, R., Segura, M., Thawani, N., Tam, M. and Stevenson, M.M. (2006)

Interaction of mouse dendritic cells and malaria-parasitized erythrocytes: uptake, maturation and antigen presentation. J. Immunol. 176: 441-450.

Stevenson, M.M. and Urban, B. Antigen presentation and dendritic cell biology in malaria. (2006)

(Eds. M.M. Stevenson and F. Zavala) Parasite Immunol. 28: 5-14.

Stevenson, M.M. and Zavala, F. (2006)

Editorial: Immunology of malarial infections. (Eds. M.M. Stevenson and F. Zavala) Parasite Immunol. 28: 1-4.

Su, Z., Segura, M, Morgan, K., Loredo-Osti, J.C. and Stevenson, M.M. (2005)

Impairment of protective immunity to blood-stage malaria by concurrent nematode infection. Infect. Immun. 73: 3531-3539.

Ing, R., Gros, P., and Stevenson, M.M. (2005)

Interleukin-15 enhances innate and adaptive immune responses to blood-stage malaria infection in mice. Infect. Immun. 73: 3172-3177.

Min-Oo, G., Fortin, A., Tam, M.-F., Gros, P., and Stevenson, (2004)

M.M. Phenotypic expression of pyruvate kinase deficiency and protection against malaria in a mouse model. Genes Immun. 5: 168-1

Chang, K.-H., Tam, M.F. and Stevenson, M.M. (2004)

.Modulation of the course and outcome of blood-stage malaria by erythropoietin-induced reticulocytosis. J. Infect. Dis. 189: 735-743.

Chang, K.-H. and Stevenson, M.M.(2004)

Malarial anemia: mechanisms and implications of insufficient erythropoiesis during blood-stage malarial. Int. J. Parasitol. In Press

Min-Oo, G., Fortin, A., Tam, M.-F., Gros, P., and Stevenson, M.M. (2004)

Resistance to blood-stage malaria in mouse strains ACB55 and ACB61 is associated with constitutive reticulocytosis and extramedullary erythropoiesis. Genes and Immunity 5: 168-175.

Richard, R.E., Weinreich, M., Chang, K.-H., Ieremia, J., Stevenson, M.M. and Blau, C. (2004)

Modulating erythrocyte mixed chimerism in a mouse model of pyruvate kinase deficiency. (Prepublished online as Blood First Edition Paper 26 February 2004; DOI 10.1182/blood-2003-10-3705), Blood 103: In Press June 15.

Chang, K.-H., Tam, M.F. and Stevenson, M.M. (2004)

Inappropriately low reticulocytosis in severe malarial anemia correlates with suppression in the development of late erythroid precursors. Blood 103: 3727-3735.

Chang, K.-H. and Stevenson, M.M. (2004)

Effect of anemia and renal cytokine production on erythropoietin production during blood-stage malaria. Kidney Int. 65: 1640-1646.

Chang, K.-H., Tam, M.F. and Stevenson, M.M. (2004)

Erythropoietin-induced reticulocytosis significantly modulates the course and outcome of blood-stage malaria. J. Infect. Dis. 189: 735-743.

Stevenson, M.M. and Riley, E.M. (2004)

Innate immunity to malaria. Nature Rev. Immunol. 4: 169-180.

Min-Oo, G., Fortin, A., Tam, M.-F., Nantel, A., Stevenson, M.M and Gros, P. (2003)

Pyruvate kinase deficiency in mice protects against malaria. Nature Genetics 35: 357-362.

Su, Z., Tam, M.-F., Jankovic, D, and Stevenson, M.M. (2003)

Vaccination against blood-stage malaria in mice using novel immunostimulatory adjuvants. Infect. Immun. 71: 5178-5187.

Fortin, A., Stevenson, M.M. and Gros, P. (2002)

Susceptibility to malaria as a complex trait: huge pressure from a tiny creature (Invited Review). Hum. Mol. Genetics. 11: 2469-2478.

Su, Z., Fortin, A., Gros, P. and Stevenson, M.M. (2002)

Opsonin-independent phagocytosis: An effector mechanism against acute blood-stage Plasmodium chabaudi AS infection. J. Infect. Dis. 186: 1321-1329.

Guilbault, C., Stotland, P., Lachance, C., Tam, M.F., Keller, A., Thompson-Snipes, L. A., Cowley, E., Hamilton, T.A., Eidelman, D.H., Stevenson, M.M. and Radzioch, D. (2002)

Influence of gender and IL-10 deficiency on the inflammatory response during chronic lung infection with Pseudomonas aeruginosa in mice. Immunology 107: 297-305.

Sebastiani, G., Blais, V., Sancho, V., Vogel, S.N., Stevenson, M.M., Gros, P., Lapointe, J.-M., Rivest, S., and Malo, D. (2002)

Host immune response of wild-derived mice during Salmonella typhimurium infection. Infect. Immun. 70: 1997-2000.

Chang, K.-H. and Stevenson, M.M.(2002)

Comparison of murine Epo ELISA and EPO bioassay in detecting serum Epo levels during anemia associated with malaria infection. J. Immunol. Methods 262: 129-136.

Fortin, A., Stevenson, M.M., and Gros, P. (2002)

Complex genetic control of susceptibility to malaria in mice (Review). Genes and Immunity 3: 177-186.

Su, Z. and Stevenson, M.M. (2002)

IL-12 is required for antibody-mediated protective immunity against blood-stage Plasmodium chabaudi AS malaria infection in mice. J. Immunol. 168: 1348-1355.

Publications - Mary Stevenson