ArticlePLoS neglected tropical diseases2012
Clofazimine modulates the expression of lipid metabolism proteins in Mycobacterium leprae-infected macrophages.
Article in PLoS neglected tropical diseases, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Case Report: Borderline Lepromatous Leprosy Therapy Complicated by Type 1 Leprosy Reaction and Adverse Reactions with Dapsone and Clofazimine.The American journal of tropical medicine and hygiene · 2024Article
- Distinguishing the Concentration- vs. Bioaccumulation-Dependent Immunological and Metabolic Effects of Clofazimine.Pharmaceutics · 2023Article
- Analysis of Lower-Limb Ulcers in Participants with Leprosy Sequelae Using Metabolomics and 16S Ribosomal DNA Sequencing.Clinical, cosmetic and investigational dermatology · 2023Article
- Pathogenicity and virulence ofVirulence · 2022Review
- Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function.PLoS neglected tropical diseases · 2022Article
- Essential Roles of PPARs in Lipid Metabolism during Mycobacterial Infection.International journal of molecular sciences · 2021Review
- Review
- Host-Related Laboratory Parameters for Leprosy Reactions.Frontiers in medicine · 2021Review
- Article
- Potential Role of CXCL10 in Monitoring Response to Treatment in Leprosy Patients.Frontiers in immunology · 2021Article
- Lipid Droplets: A Significant but Understudied Contributor of Host⁻Bacterial Interactions.Cells · 2019Review
- Optimized Background Regimen for Treatment of Active Tuberculosis with the Next-Generation Benzothiazinone Macozinone (PBTZ169).Antimicrobial agents and chemotherapy · 2018Article
- Article
- Efficacy of Rifampin Plus Clofazimine in a Murine Model of Mycobacterium ulcerans Disease.PLoS neglected tropical diseases · 2015Article
- Leprosy in the 21st century.Clinical microbiology reviews · 2015Review
- Rapid preparation of high-purity nuclear proteins from a small number of cultured cells for use in electrophoretic mobility shift assays.BMC immunology · 2014Article
- Mycobacterium leprae intracellular survival relies on cholesterol accumulation in infected macrophages: a potential target for new drugs for leprosy treatment.Cellular microbiology · 2014Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycobacterium leprae (M. leprae) lives and replicates within macrophages in a foamy, lipid-laden phagosome. The lipids provide essential nutrition for the mycobacteria, and M. leprae infection modulates expression of important host proteins related to lipid metabolism. Thus, M. leprae infection increases the expression of adipophilin/adipose differentiation-related protein (ADRP) and decreases hormone-sensitive lipase (HSL), facilitating the accumulation and maintenance of lipid-rich environments suitable for the intracellular survival of M. leprae. HSL levels are not detectable in skin smear specimens taken from leprosy patients, but re-appear shortly after multidrug therapy (MDT). This study examined the effect of MDT components on host lipid metabolism in vitro, and the outcome of rifampicin, dapsone and clofazimine treatment on ADRP and HSL expression in THP-1 cells. Clofazimine attenuated the mRNA and protein levels of ADRP in M. leprae-infected cells, while those of HSL were increased. Rifampicin and dapsone did not show any significant effects on ADRP and HSL expression levels. A transient increase of interferon (IFN)-β and IFN-γ mRNA was also observed in cells infected with M. leprae and treated with clofazimine. Lipid droplets accumulated by M. leprae-infection were significantly decreased 48 h after clofazimine treatment. Such effects were not evident in cells without M. leprae infection. In clinical samples, ADRP expression was decreased and HSL expression was increased after treatment. These results suggest that clofazimine modulates lipid metabolism in M. leprae-infected macrophages by modulating the expression of ADRP and HSL. It also induces IFN production in M. leprae-infected cells. The resultant decrease in lipid accumulation, increase in lipolysis, and activation of innate immunity may be some of the key actions of clofazimine.
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