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Leishmania donovani-specific 25- and 28-kDa urinary proteins activate macrophage effector functions, lymphocyte proliferation and Th1 cytokines production

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Abstract

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.

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Acknowledgements

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.

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Correspondence to Rakesh K. Singh.

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Kumar, V., Gour, J.K., Singh, N. et al. Leishmania donovani-specific 25- and 28-kDa urinary proteins activate macrophage effector functions, lymphocyte proliferation and Th1 cytokines production. Parasitol Res 112, 1427–1435 (2013). https://doi.org/10.1007/s00436-013-3272-z

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