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Please use this identifier to cite or link to this item: http://hdl.handle.net/1993/3920

Title: The role of parasite-derived arginase in murine Leishmania major
Authors: Muleme, Helen
Supervisor: Uzonna, Jude (Immunology)
Examining Committee: Soussi Gounni, Abdel (Immunology) Wilkins, John (Biochemistry and Medical Genetics) Anderson, Robert (University of Winnipeg)
Graduation Date: May 2010
Keywords: arginase
leishmaniasis
immunoparasitology
Issue Date: 8-Apr-2010
Citation: Muleme HM, Reguera RM, Berard A, Azinwi R, Jia P, Okwor IB, Beverley S, Uzonna JE (2009). Infection with arginase-deficient Leishmania major reveals a parasite number-dependent and cytokine-independent regulation of host cellular arginase activity and disease pathogenesis, Journal of Immunology 183(12):8068-76
Abstract: The outcome of infection with Leishmania major depends in part on the balance between arginase and inducible nitric oxide synthase in macrophages. These enzymes compete for the substrate L-arginine. Leishmania major also encodes an arginase gene but, the role of this parasite-derived enzyme in infection remains unclear. We hypothesize that parasite-derived arginase influences parasite survival and host immune response to L. major. To examine this hypothesis, we employed an arginase deficient null mutant L. major in in vitro and in vivo experiments. Our results show that deficiency of parasite-derived arginase impaired parasite proliferation and disease pathogenesis. Increased arginase activity however neither affected nitric oxide production, nor did it correlate with IL-4 production. Primary infection of normally resistant hosts causes a chronic infection and does not protect them against re-infection. Thus, parasite-derived arginase is of nutritional importance to L. major, but is not a feasible therapeutic drug target.
URI: http://hdl.handle.net/1993/3920
Appears in Collection(s):FGS - Electronic Theses & Dissertations (Public)

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