The role of parasite-derived arginase in murine Leishmania major

dc.contributor.authorMuleme, Helen
dc.contributor.examiningcommitteeSoussi Gounni, Abdel (Immunology) Wilkins, John (Biochemistry and Medical Genetics) Anderson, Robert (University of Winnipeg)en
dc.contributor.supervisorUzonna, Jude (Immunology)en
dc.date.accessioned2010-04-08T19:47:34Z
dc.date.available2010-04-08T19:47:34Z
dc.date.issued2010-04-08T19:47:34Z
dc.degree.disciplineImmunologyen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractThe 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.en
dc.description.noteMay 2010en
dc.format.extent1547869 bytes
dc.format.mimetypeapplication/pdf
dc.identifier.citationMuleme 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):8068-76en
dc.identifier.urihttp://hdl.handle.net/1993/3920
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectarginaseen
dc.subjectleishmaniasisen
dc.subjectimmunoparasitologyen
dc.titleThe role of parasite-derived arginase in murine Leishmania majoren
dc.typemaster thesisen_US
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