The role of parasite-derived arginase in murine Leishmania major
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.
arginase, leishmaniasis, immunoparasitology
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