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Intertwining of Retinoic Acid and Cholesterol Pathway and its Consequences in Leishmania donovani-Infected Macrophages

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Pathobiology of Parasitic Protozoa: Dynamics and Dimensions

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Abstract

Visceral leishmaniasis (VL) is the most severe disease among other forms of leishmaniasis and results in a fatality in more than 90% of cases if left untreated. It is a zoonotic disease caused by Leishmania donovani and is prevalent in the Indian subcontinent, affecting the population of poor socioeconomic backgrounds. People residing in endemic regions lacking proteins, iron, zinc, and vitamin A in their diet are more prone to develop this opportunist infection into a full-blown disease. The deficiency of a prominent micronutrient vitamin A favors the parasites to develop an infection in the human host, and WHO recommends 200,000 IU doses of vitamin A to VL patients on admission. Additionally, Leishmania entry to the host is favored by cholesterol present in the plasma membrane, and survival inside the host is achieved by utilizing host cholesterol as Leishmania and other trypanosomatids lack de novo synthesis of sterol. However, in our study, we have already reported that a deficit of retinoic acid (RA), a metabolite of vitamin A, favors the parasite to increase their number in L. donovani-infected macrophages by downregulating immune response. Along with this finding, we have also observed the restoration of cellular cholesterol levels in L. donovani-infected macrophages by RA. In this chapter, we have explained the connecting link between cholesterol and RA in visceral leishmaniasis.

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  1. Department of Biotechnology, Motilal Nehru National Institute of Technology Allahabad, Prayagraj, UP, India

    Satya Prakash & Ambak Kumar Rai

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  1. School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India

    Budhaditya Mukherjee

  2. Department of Microbiology, Adamas University, Jagannathpur, West Bengal, India

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  3. Johns Hopkins University, Baltimore, MD, USA

    Rupkatha Mukhopadhyay

  4. Federal University of Piauí, Piauí, Brazil

    Bruno Guedes Alcoforado Aguiar

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Prakash, S., Rai, A.K. (2023). Intertwining of Retinoic Acid and Cholesterol Pathway and its Consequences in Leishmania donovani-Infected Macrophages. In: Mukherjee, B., Bhattacharya, A., Mukhopadhyay, R., Aguiar, B.G.A. (eds) Pathobiology of Parasitic Protozoa: Dynamics and Dimensions. Springer, Singapore. https://doi.org/10.1007/978-981-19-8225-5_2

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