ArticlePLoS neglected tropical diseases2020
Glutamine supplementation improves the efficacy of miltefosine treatment for visceral leishmaniasis.
Article in PLoS neglected tropical diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth ofVirulence · 2025Article
- Integrated subtractive genomics and structure-based approach to unravel the therapeutic drug target of Leishmania species.Archives of microbiology · 2024Article
- The intersection of hostMicrobiology and molecular biology reviews : MMBR · 2024Review
- Effects of Leishmania major infection on the gut microbiome of resistant and susceptible mice.Applied microbiology and biotechnology · 2024Article
- Metabolomics analysis of visceral leishmaniasis based on urine of golden hamsters.Parasites & vectors · 2023Article
- Glutamine Metabolism Supports the Functional Activity of Immune Cells against Aspergillus fumigatus.Microbiology spectrum · 2023Article
- Similarities and divergences in the metabolism of immune cells in cancer and helminthic infections.Frontiers in oncology · 2023Review
- Article
- Putrescine supplementation shifts macrophage L-arginine metabolism related-genes reducing Leishmania amazonensis infection.PloS one · 2023Article
- An integrated study of glutamine alleviates enteritis induced by glycinin in hybrid groupers using transcriptomics, proteomics and microRNA analyses.Frontiers in immunology · 2023Article
- Article
- Transcriptional profiling of macrophages reveals distinct parasite stage-driven signatures during early infection by Leishmania donovani.Scientific reports · 2022Article
- Myeloma-derived IL-32γ induced PD-L1 expression in macrophages facilitates immune escape via the PFKFB3-JAK1 axis.Oncoimmunology · 2022Article
- Differential Inhibition of HIV Replication by the 12 Interferon Alpha Subtypes.Journal of virology · 2021Article
- Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused byPathogens (Basel, Switzerland) · 2021Article
- Tryp-ing Up Metabolism: Role of Metabolic Adaptations in Kinetoplastid Disease Pathogenesis.Infection and immunity · 2021Review
- Deletion of Glutamine Synthetase Gene Disrupts the Survivability and Infectivity ofFrontiers in cellular and infection microbiology · 2021Article
- Glutamine reliance in cell metabolism.Experimental & molecular medicine · 2020Review
- An Army Marches on Its Stomach: Metabolic Intermediates as Antimicrobial Mediators inFrontiers in cellular and infection microbiology · 2020Review
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe 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.
methodsWe 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.
findingsWe 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.
conclusionsOur data indicates that dietary glutamine supplementation may act as a promising adjuvant for the treatment of visceral leishmaniasis.
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