ArticleJournal of lipid research2012
Hyperlipidemia offers protection against Leishmania donovani infection: role of membrane cholesterol.
Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Ontogeny independent expression of LPCAT2 in granuloma macrophages during experimental visceral leishmaniasis.Communications biology · 2026Article
- Sterol Endoperoxides and Their Antileishmanial Effects: Influence on Viability, Oxygen Metabolism and Sterol Synthesis.Molecules (Basel, Switzerland) · 2026Article
- Scrutinized lipid utilization disrupts Amphotericin-B responsiveness in clinical isolates ofeLife · 2025Article
- Integration of hepatic lipidomics and transcriptomics reveals dysregulation of lipid metabolism in a golden hamster model of visceral leishmaniasis.Frontiers in immunology · 2025Article
- Non-additive strong gene interactions cause striking differences in organ pathology and cytokine response in Leishmaniasis.Frontiers in immunology · 2025Article
- Oxidative stress-driven enhanced iron production and scavenging through Ferroportin reorientation worsens anemia in antimony-resistant Leishmania donovani infection.PLoS pathogens · 2025Article
- Leishmania protein KMP-11 modulates cholesterol transport and membrane fluidity to facilitate host cell invasion.EMBO reports · 2024Article
- Unmasking the Mechanism behind Miltefosine: Revealing the Disruption of Intracellular CaBiomolecules · 2024Review
- Non-Vesicular Lipid Transport Machinery inInternational journal of molecular sciences · 2023Review
- Fatty Acid Composition and Metabolism inInternational journal of molecular sciences · 2023Review
- Data Independent Acquisition Reveals In-Depth Serum Proteome Changes in Canine Leishmaniosis.Metabolites · 2023Article
- Systems biology of autophagy in leishmanial infection and its diverse role in precision medicine.Frontiers in molecular biosciences · 2023Review
- Impact of Visceral Leishmaniasis on Local Organ Metabolism in Hamsters.Metabolites · 2022Article
- Mass spectrometry imaging identifies altered hepatic lipid signatures during experimentalFrontiers in immunology · 2022Article
- Host cholesterol influences the activity of sterol biosynthesis inhibitors in Leishmania amazonensis.Memorias do Instituto Oswaldo Cruz · 2022Article
- Association between Hypertriglyceridemia and Disease Severity in Visceral Leishmaniasis.The American journal of tropical medicine and hygiene · 2021Article
- Hepatomegaly Associated with Non-Obstructive Sinusoidal Dilation in Experimental Visceral Leishmaniasis.Pathogens (Basel, Switzerland) · 2021Article
- Balancing de novo synthesis and salvage of lipids by Leishmania amastigotes.Current opinion in microbiology · 2021Review
- The Inflammatory Effects of Dietary Lipids Regulate Growth of Parasites during Visceral Leishmaniasis.mSphere · 2021Article
- Tryp-ing Up Metabolism: Role of Metabolic Adaptations in Kinetoplastid Disease Pathogenesis.Infection and immunity · 2021Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leishmania donovani (LD), the causative agent of visceral leishmaniasis (VL), extracts membrane cholesterol from macrophages and disrupts lipid rafts, leading to their inability to stimulate T cells. Restoration of membrane cholesterol by liposomal delivery corrects the above defects and offers protection in infected hamsters. To reinforce further the protective role of cholesterol in VL, mice were either provided a high-cholesterol (atherogenic) diet or underwent statin treatment. Subsequent LD infection showed that an atherogenic diet is associated with protection, whereas hypocholesterolemia due to statin treatment confers susceptibility to the infection. This observation was validated in apolipoprotein E knockout mice (AE) mice that displayed intrinsic hypercholesterolemia with hepatic granuloma, production of host-protective cytokines, and expansion of antileishmanial CD8(+)IFN- γ (+) and CD8(+)IFN- γ (+)TNF- α (+) T cells in contrast to the wild-type C57BL/6 (BL/6) mice when infected with LD. Normal macrophages from AE mice (N-AE-MΦ) showed 3-fold higher membrane cholesterol coupled with increased fluorescence anisotropy (FA) compared with wild-type macrophage (N-BL/6-MΦ). Characterization of in vitro LD-infected AE macrophage (LD-AE-MΦ) revealed intact raft architecture and ability to stimulate T cells, which were compromised in LD-BL/6-MΦ. This study clearly indicates that hypercholesterolemia, induced intrinsically or extrinsically, can control the pathogenesis of VL by modulating immune repertoire in favor of the host.
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