Abstract
Leishmania silently evades host immune system and establish in the hostile environment of host macrophage phagolysosomes. For differentiation, growth and division parasite acquires divalent cations especially iron from the host nutritive pool. Natural resistance associated with macrophage protein1 (NRAMP1), a cation transporter that effluxes out divalent cations specifically iron from phagosomal milieu to the cytosol, to create ions deprived status for pathogenic microorganisms. The mechanisms of NRAMP1 regulation are largely unknown in leishmanial infections. In the present study, we identified a secretory Leishmania donovani peroxidase (Prx) that showed peroxidoxin like peroxidase activity and significantly reduced H2O2, O2.− and NO levels in LPS activated macrophages. Further, we also observed down regulated Nramp1 expression and concomitantly declined labile iron pool in activated macrophages treated with identified peroxidase. Prx also decreased levels of TNF-α, IFN-γ and IL-12 in LPS activated macrophages. These observations indicate a bifunctional protective role of secretory Prx; first it reduces redox activation of macrophages, and secondly it allows iron access to Leishmania by down regulating NRAMP1 expression.
Highlights
Leishmaniases, caused by an obligate intracellular protozoan parasite of the genus Leishmania, are endemic in more than 98 countries of tropical and temperate regions [1,2]
About 20 species of Leishmania are responsible for three clinical forms i.e. visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL)
The present study demonstrates one of the probable survival strategies of Leishmania species in the host macrophages
Summary
Leishmaniases, caused by an obligate intracellular protozoan parasite of the genus Leishmania, are endemic in more than 98 countries of tropical and temperate regions [1,2]. About 20 species of Leishmania are responsible for three clinical forms i.e. visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL). The annual global prevalence of all forms of leishmaniasis is nearly 10 million and approximately 350 million people are at risk. There is a gross underreporting of the cases from endemic regions and these figures may go up [4,5,6]. Leishmaniasis is occupying pandemic status due to population migration from endemic to non-endemic regions though current statistical data are lacking in disease endemic countries [7]
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