Ferreira, C and Mesquita, I and Barbosa , AM and Osório, NS and Torrado , E and Beauparlant , CJ and Droit, A and Cunha, C and Carvalho , A and Saha, B and Estaquier, J and Silvestre, R (2020) Glutamine supplementation improves the efficacy of miltefosine treatment for visceral leishmaniasis. PLoS Neglected Tropical Diseases., 14 (3). e0008125. .

Text 19. Dr. Saha B. (PLoS Neg. Tro. Dis) open access.pdf Restricted to Repository staff only Download (2435Kb) | Request a copy

Abstract

Background The disturbance of host metabolic pathways by Leishmania parasites has crucial consequences for the activation status of immune cells and the outcome of infection. Glutamine has been described as an immunomodulatory amino acid, yet its role during Leishmania infection is still unknown. Methods We performed transcriptomics in uninfected and L. donovani-infected macrophages 6 hours post-infection. Glutamine quantification by HPLC was assessed in the supernatant of macrophages throughout the infection course. For experimental L. donovani infections, mice were infected with 1.0 x 108 stationary L. donovani promastigotes. Glutaminase (GLS) chemical inhibition was performed using BPTES and glutamine was administered throughout infection. For combined therapy experiment, a daily administration of miltefosine and glutamine was performed by oral gavage. Parasite burden was determined using a Taqman-based assay. Immune cell phenotyping and cytotoxicity were performed in splenic cells using flow cytometry. Findings We show that glutamine is essential for the control of L. donovani infection. Transcriptomic analysis of L. donovani-infected macrophages demonstrated an upregulation of genes involved in glutamine metabolism. Pharmacological inhibition of glutaminolysis significantly increased the susceptibility to infection, accompanied by an increased recruitment of anti-inflammatory myeloid cells and impaired T cell responses. Remarkably, the supplementation of glutamine to mice infected with L. donovani during miltefosine treatment potentiates parasite clearance through the development of a more effective anti-Leishmania adaptive immune response. Conclusions Our data indicates that dietary glutamine supplementation may act as a promising adjuvant for the treatment of visceral leishmaniasis.

Item Type:	Article
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	26 Aug 2020 10:12
Last Modified:	06 Dec 2021 11:54
URI:	http://nccs.sciencecentral.in/id/eprint/808

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