Identification of Th1-responsive leishmanial excretory-secretory antigens (LESAs)

The objective of this study was to evaluate the immunomodulatory role of leishmanial excretory-secretory antigens (LESAs) released by in vitro cultured protozoan parasite Leishmania donovani promastigotes. A total of seventeen excretory-secretory proteins of relative molecular weights 11, 13, 16, 18, 21, 23, 26, 29, 33, 35, 42, 51, 54, 58, 64, 70 and 80 kDa were identified. The proteins were divided into five fractions (F1-F5) along with the whole LESAs, these fractions were evaluated for their potential antigenicity to induce macrophage effector functions, lymphoproliferation and cytokines production capabilities. Two fractions, F1 (11, 13 and 16 kDa) and F3 (26, 29 and 33 kDa), were found to be highly immunogenic as they significantly induced NADPH oxidase and SOD activities as well as NOx, TNF-α, IFN-γ and IL-12 production in stimulated RAW 264.7 macrophages. Further, these antigens also induced significant proliferation of human peripheral blood mononuclear cells along with increased production of IFN-γ and IL-12. The results strongly suggest the potential role of LESAs in the modulation of macrophage effector functions and Th1 immune response that gives a hope to develop potent vaccine for visceral leishmaniasis.