Date of Award
Doctor of Philosophy
Douglas E. Jones
The in vivo differential killing of L. amazonensis and L. major in C3H mice were reflected in vitro using BMM under identical activation conditions. We have shown that this delayed intracellular L. amazonensis killing when compared to L. major, occurred under conditions of similar levels of NO and iNOS. Only when superoxide was induced in the presence of NO, was L. amazonensis killed in vitro to a similar level as L. major. This results indicates not only the host immune response to the two species of Leishmania is different, but also the requirements for their intracellular killing are different. Intracellular killing of L. amazonensis amastigotes inside macrophages was induced by the addition of DLN cells from L. major infected mice. This L. major antigen-specific DLN cell activation of BMM was induced by a combination of CD4+ T cells and B cells, by which the intracellular L. amazonensis killing in this system was dependent on secreted factors including antibody and superoxide production. The antibody dependent killing of L. amazonensis was not reproducible using immune serum alone or with either IFN-gamma or CD4+ T cells from L. major cells infected mice. These results indicate that other factors are needed in addition to antibody to induce intracellular parasite killing. The factors needed may be required to induce effective macrophages antibody receptor (FcR) expression and promote macrophage activation and superoxide secretion. Leishmania infection of macrophages influenced FcR expression of these receptors by downregulating the mRNA expression of the activator FcgammaI receptor (CD64) and upregulating the mRNA expression of the inhibitory receptor FcgammaRII (CD32). DLN cells from L. major secrete factor(s) to downregulate CD32 mRNA expression and at the same time induces the mRNA expression of CD64 in a balance to allow macrophage activation by antibodies and induction of superoxide to kill intracellular L. amazonensis amastigotes. These studies emphasis the necessity to have superoxide as a key factor, in the presence of nitric oxide, to kill L. amazonensis and it is seems that one of the major resistance strategies for L. amazonensis survival inside the macrophages is to prevent superoxide production.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Rami Mahmoud Mukbel
Mukbel, Rami Mahmoud, "Leishmania amazonensis and macrophage interactions: immune factors necessary to kill the parasite " (2005). Retrospective Theses and Dissertations. 1841.