Journal Article

The effect of treatment with a non-ionic surfactant vesicular formulation of sodium stibogluconate on host immune responses and serum metabolites in a murine model of Leishmania donovani

van Reenen, Mari, Opare, Priscilla Abena Ankamaa, Carter, Katharine C., Cele, Zama, Osero, Bernard Ong’ondo, Hurdayal, Ramona, Aruleba, Raphael Taiwo, Loots, Du Toit, Luies, Laneke, Brombacher, Frank

2025

Overview

Visceral leishmaniasis (VL), caused by , is associated with parasite-induced immunological and physiological changes that ensure the survival of amastigotes within the host. Both the parasite and the host have nutritional requirements, and for auxotrophic , dependence on the host to supply specific growth requirements is essential. This highlights an intricate link between host immunity and metabolism during VL. This study explores the interplay between the host metabolome and immune responses pre- and post-infection and treatment, aiming to identify early metabolite markers of therapeutic success against . BALB/c mice infected with were divided into cured and non-cured groups based on treatment with a non-ionic surfactant vesicle formulation of sodium stibogluconate (300 mg Sb /kg, SSG-NIV) or PBS vehicle control. Specific immune responses were determined at day 21 and day 60 post-infection, and serum metabolite levels was measured using untargeted GC×GC-TOFMS metabolomics. Treatment effectively reduced parasite loads, triggering heightened CD4+ and CD8+ T-cell responses at day 21, with increased IFN-γ, IL-12, and IL-4, and decreased IL-10 and TGF-β. Pre-treatment metabolomics analysis identified changes in glycolysis, fatty acid and amino acid metabolism 1-week PI, suggesting an increased Warburg effect to supplement parasite survival and initiation of immune responses. Valine, lactic acid, and glycerol-1-oleate were identified as markers of early infection. Treatment with SSG-NIV altered metabolism of major macromolecules and the TCA cycle relative to non-cured groups. Additionally, glycine and ribitol show promise as immune correlates for antiparasitic therapies. These findings highlight the diagnostic and prognostic potential of serum-derived metabolites in monitoring host immune responses to VL and treatment.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Amastigotes / Amino acids / Animal models / Animals / Antimony Sodium Gluconate - administration & dosage / Antimony Sodium Gluconate - chemistry / Antimony Sodium Gluconate - pharmacology / Antiparasitic agents / Biomarkers / Biomarkers - blood / Bone marrow / CD4 antigen / CD8 antigen / chemotherapy / Clinical outcomes / Disease Models, Animal / Drug dosages / Female / Glycolysis / Host-parasite interactions / Immune response / immunity / Immunology / Infections / Interleukins / Laboratory animals / Leishmania / Leishmania donovani / Leishmania donovani - drug effects / Leishmania donovani - immunology / Leishmaniasis, Visceral - blood / Leishmaniasis, Visceral - drug therapy / Leishmaniasis, Visceral - immunology / Leishmaniasis, Visceral - metabolism / Leishmaniasis, Visceral - parasitology / Lymphocytes T / Metabolism / Metabolites / Metabolome - drug effects / Metabolomics / Metabolomics - methods / Mice / Mice, Inbred BALB C / mouse / Nutrient requirements / Parasites / Parasitic diseases / Sodium stibogluconate / Spleen / Surface-Active Agents - chemistry / Surface-Active Agents - pharmacology / Surfactants / Transforming growth factor-b / Tricarboxylic acid cycle / Tropical diseases / Valine / Visceral leishmaniasis / γ-Interferon