Leishmania donovani-specific 25- and 28-kDa urinary proteins activate macrophage effector functions, lymphocyte proliferation and Th1 cytokines production
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Growing incidence of drug resistance against leishmaniasis in endemic areas and limited drug options necessitates the need for a vaccine. Notwithstanding significant leishmanial research in the past decades, a vaccine candidate is far from reality. In this study, we report the potential of two urinary leishmanial proteins to induce macrophage effector functions, inflammatory cytokines production and human lymphocytes proliferation. A total four proteins of molecular mass 25, 28, 54 and 60 kDa were identified in human urine samples. The 25 and 28 kDa proteins significantly induced NADPH oxidase (p < 0.001), superoxide dismutase (p < 0.001) and inducible nitric oxide synthase (p < 0.001) activities in stimulated RAW264.7 macrophages. The release of nitric oxide, tumor necrosis factor-alpha and interleukin (IL)-12 was also significantly (p < 0.001) higher in 25 and 28 kDa activated macrophages as compared with cells activated with other two proteins. These two proteins also induced significant (p < 0.001) proliferation and release of IFN-γ and IL-12 in human peripheral blood mononuclear cells.
Financial assistance received from Council of Scientific and Industrial Research (No. 27(0183)/08/EMR-II), New Delhi, India, and Department of Biotechnology (BT/PR11177/MED/29/2008), New Delhi, India, is greatly acknowledged. The authors VK, JKG, SB and NS are thankful to CSIR, UGC, CSIR and DBT, New Delhi, respectively, for their research fellowships.
Conflict of interest
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