ArticlePLoS neglected tropical diseases2016
Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy.
Article in PLoS neglected tropical diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Visceral leishmaniasis: an integrated review of resistance mechanisms, host immunometabolism, and next generation therapeutics.Inflammopharmacology · 2026Review
- Phylogenetic analysis of amino acid sequences indicates a central role of transmembrane domain structural elements in MHC class II function.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Lipid accumulation in tuberculosis granulomas inhibits macrophage-CD4Nature microbiology · 2026Article
- Cholesterol Efflux Decreases TLR4-Target Gene Expression in Cultured Macrophages Exposed toMicroorganisms · 2024Article
- Targeting and activation of macrophages in leishmaniasis. A focus on iron oxide nanoparticles.Frontiers in immunology · 2024Review
- The Application of MD Simulation to Lead Identification, Vaccine Design, and Structural Studies in Combat against Leishmaniasis - A Review.Mini reviews in medicinal chemistry · 2024Review
- Ubiquitination of Major Histocompatibility Complex II Changes Its Immunological Recognition Structure.International journal of molecular sciences · 2023Article
- Host Lipid Manipulation by Intracellular Bacteria: Moonlighting for Immune Evasion.The Journal of membrane biology · 2023Review
- Transcriptional Profiling ofMicroorganisms · 2022Article
- Revisiting the Principles of Designing a Vaccine.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Efficient Cholesterol Transport in Dendritic Cells Defines Optimal Exogenous Antigen Presentation and Toxoplasma gondii Proliferation.Frontiers in cell and developmental biology · 2022Article
- Modulation of Cholesterol Pathways in Human Macrophages Infected by Clinical Isolates ofFrontiers in cellular and infection microbiology · 2022Article
- Role of Cytokines in Experimental and Human Visceral Leishmaniasis.Frontiers in cellular and infection microbiology · 2021Review
- Determinants of Innate Immunity in Visceral Leishmaniasis and Their Implication in Vaccine Development.Frontiers in immunology · 2021Review
- Glutamine supplementation improves the efficacy of miltefosine treatment for visceral leishmaniasis.PLoS neglected tropical diseases · 2020Article
- Review
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- Structure, Topology, and Dynamics of Membrane-Inserted Polypeptides and Lipids by Solid-State NMR Spectroscopy: Investigations of the Transmembrane Domains of the DQ Beta-1 Subunit of the MHC II Receptor and of the COP I Protein p24.Frontiers in molecular biosciences · 2019Article
- Leishmania donovani reduces the levels of retinoic acid-synthesizing enzymes in infected macrophages and favoring its own survival.Parasitology research · 2019Article
- Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPreviously we reported that Kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. Splenic macrophages (MΦ) of Leishmania donovani (LD) infected mice show decrease in membrane cholesterol, while LD infected macrophages (I-MΦ) show defective T cell stimulating ability that could be corrected by liposomal delivery of cholesterol. T helper cells recognize peptide antigen in the context of class II MHC molecule. It is known that the conformation of a large number of membrane proteins is dependent on membrane cholesterol. In this investigation we tried to understand the influence of decreased membrane cholesterol in I-MΦ on the conformation of MHC-II protein and peptide-MHC-II stability, and its bearing on the antigen specific T-cell activation. METHODOLOGY/PRINCIPAL
findingsMΦ of CBA/j mice were infected with Leishmania donovani (I-MΦ). Two different anti-Aκ mAbs were used to monitor the status of MHC-II protein under parasitized condition. One of them (11.5-2) was conformation specific, whereas the other one (10.2.16) was not. Under parasitized condition, the binding of 11.5-2 decreased significantly with respect to the normal counterpart, whereas that of 10.2.16 remained unaltered. The binding of 11.5-2 was restored to normal upon liposomal delivery of cholesterol in I-MΦ. By molecular dynamics (MD) simulation studies we found that there was considerable conformational fluctuation in the transmembrane domain of the MHC-II protein in the presence of membrane cholesterol than in its absence, which possibly influenced the distal peptide binding groove. This was evident from the faster dissociation of the cognate peptide from peptide-MHC complex under parasitized condition, which could be corrected by liposomal delivery of cholesterol in I-MΦ.
conclusionThe decrease in membrane cholesterol in I-MΦ may lead to altered conformation of MHC II, and this may contribute to a faster dissociation of the peptide. Furthermore, liposomal delivery of cholesterol in I-MΦ restored its normal antigen presenting function. This observation brings strength to our previous observation on host directed therapeutic application of liposomal cholesterol in experimental visceral leishmaniasis.
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