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Solute carrier protein family 11 member 1 (Slc11a1) activation efficiently inhibits Leishmania donovani survival in host macrophages

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Abstract

Visceral leishmaniasis (kala-azar), a life threatening disease caused by L. donovani, is a latent threat to more than 147 million people living in disease endemic South East Asia region of the Indian subcontinent. The therapeutic option to control leishmanial infections are very limited, and at present comprise only two drugs, an antifungal amphotericin B and an antitumor miltefosine, which are also highly vulnerable for parasitic resistance. Therefore, identification and development of alternate control measures is an exigent requirement to control leishmanial infections. In this study, we report that functionally induced expression of solute carrier protein family 11 member 1 (Slc11a1), a transmembrane divalent cationic transporter recruited on the surface of phagolysosomes after phagocytosis of parasites, effectively inhibits Leishmania donovani growth in host macrophages. Further, the increased Slc11a1 functionality also resulted in increased production of NOx, TNF-α and IL-12 by activated macrophages. The findings of this study signify the importance of interplay between Slc11a1 expression and macrophages activation that can be effectively used to control of Leishmania growth and survival.

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Acknowledgements

Financial support from Department of Science and Technology, New Delhi (SB/SO/HS/0091/2013) is greatly acknowledged. The authors MGR and NT are extremely thankful to BHU and UGC, New Delhi, respectively for their research fellowships.

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Author notes

  1. Nisha Singh

    Present address: Departement of Biochemistry, HNB University, Srinagar, Uttrakhand, 246174, India

  2. Surabhi Bajpai

    Present address: Department of Bioscience and Biotechnolgy, Banasthali University, Banasthali, Tonk, Rajasthan, 304022, India

Authors and Affiliations

  1. Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India

    Nisha Singh, Mallikarjuna Rao Gedda, Neeraj Tiwari, Suya P. Singh, Surabhi Bajpai & Rakesh K. Singh

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  1. Nisha Singh
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  2. Mallikarjuna Rao Gedda
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  3. Neeraj Tiwari
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  6. Rakesh K. Singh
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Correspondence to Rakesh K. Singh.

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Singh, N., Gedda, M.R., Tiwari, N. et al. Solute carrier protein family 11 member 1 (Slc11a1) activation efficiently inhibits Leishmania donovani survival in host macrophages. J Parasit Dis 41, 671–677 (2017). https://doi.org/10.1007/s12639-016-0864-4

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  • DOI: https://doi.org/10.1007/s12639-016-0864-4

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