Retinoic Acid Increases Cellular Cholesterol in Leishmania donovani-Infected Macrophages in an mTOR-Independent Manner

Prakash, Satya; Kumar, Ambak

doi:10.1128/spectrum.02699-22

Cited by 6 publications

(3 citation statements)

References 23 publications

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“…We searched some genes related to lipid transport, some scavenger receptors shown in Leishmania infection models ( 25 , 26 ). Lower expression of CETP mRNA was observed in the Leishmania infection in the 4th and 12th weeks compared with the control without infection ( Figure 11A ).…”

Section: Resultsmentioning

confidence: 99%

The impact of cholesteryl ester transfer protein on the progression of cutaneous leishmaniasis

Batista-Dantas,

Ozaki,

Santana

et al. 2024

Front. Immunol.

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IntroductionPathogenesis of cutaneous leishmaniases involves parasite growth, persistent inflammation, and likely participation of lipoproteins (LP). The cholesteryl ester transfer protein (CETP), involved in LP remodeling, has been shown to participate in the inflammatory response and the evolution of infectious conditions. MethodsWe evaluated the impact of the presence of CETP on infection by Leishmania (L.) amazonensis in an experimental model of cutaneous leishmaniasis using C57BL6/J mice transgenic for human CETP (CETP), having as control their littermates that do not express the protein, wild-type (WT) mice. The progression of the lesion after infection in the footpad was monitored for 12 weeks. Two groups of animals were formed to collect the plantar pad in the 4th and 12th week post-infection. ResultsThe lesion increased from the 3rd week onwards, in both groups, with a gradual decrease from the 10th week onwards in the CETP group compared to the WT group, showing a reduction in parasitism and an improvement in the healing process, a reduction in CD68+ cells, and an increase in CD163+ and CD206, characterizing a population of M2 macrophages. A reduction in ARG1+ cells and an increase in INOS+ cells were observed. During infection, the LP profile showed an increase in triglycerides in the VLDL fraction in the CETP group at 12 weeks. Gene expression revealed a decrease in the CD36 receptor in the CETP group at 12 weeks, correlating with healing and parasite reduction. In vitro, macrophages derived from bone marrow cells from CETP mice showed lower parasite load at 48 h and, a reduction in arginase activity at 4 h accompanied by increased NO production at 4 and 24 h compared to WT macrophages, corroborating the in vivo findings.DiscussionThe data indicate that the presence of CETP plays an important role in resolving Leishmania (L.) amazonensis infection, reducing parasitism, and modulating the inflammatory response in controlling infection and tissue repair.

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Section: Resultsmentioning

confidence: 99%

The impact of cholesteryl ester transfer protein on the progression of cutaneous leishmaniasis

Batista-Dantas,

Ozaki,

Santana

et al. 2024

Front. Immunol.

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“…Milk extracellular vesicles could increase the abundance of "good" microbiota such as Akkermansia, Muribaculum, and Turicibacter and promote the immune related to IgA production, retinol, or D-glutamine metabolism [38]. Retinoic acid restores cholesterol levels in Leishmania donovani-infected macrophages and reduces the parasite burden in an mTOR-independent manner [39,40]. Retinoic acid-liganded RARα mediates T cell activation/quiescence metabolism and differentiation of regulatory T cell subsets through PI3K and subsequent activation of Akt and mTOR signaling pathways [41].…”

Section: Discussionmentioning

confidence: 99%

Akkermansia muciniphila Ameliorates Lung Injury in Smoke-Induced COPD Mice by IL-17 and Autophagy

Zhang

Liu

2023

Cellular Microbiology

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Objective. Smoking is a primary hazard factor for chronic obstructive pulmonary disease (COPD), which induced a decrease in intestinal Akkermansia muciniphila abundance and Th17 imbalance in COPD. This study analyzed the changes of gut microbiota metabolism and Akkermansia abundance in patients with smoking-related COPD and explored the potential function of Akkermansia muciniphila in smoke-induced COPD mice. Methods. Gut microbiota diversity and metabolic profile were analyzed by 16S rRNA sequence and metabolomics in COPD patients. The IL-1β, IL-17, TNF-α, and IL-6 levels were tested by ELISA. Lung tissue damage was observed by HE staining. The expression of cleave-caspase 3, trophoblast antigen 2 (TROP2), and LC3 in lung tissues were analyzed by IHC or IF. The p-mTOR, mTOR, p62, and LC3 expression in lung tissues were tested by western blot. Results. The levels of IL-17, IL-1β, TNF-α, and IL-6 in the peripheral blood of COPD patients increased significantly. The number and alpha diversity of gut microbiota were decreased in COPD patients. The abundance of Akkermansia muciniphila in gut of COPD patients was decreased, and the metabolic phenotype and retinol metabolism were changed. In the retinol metabolism, the retinol and retinal were significantly changed. Akkermansia muciniphila could improve the alveolar structure and inflammatory cell infiltration in lung tissue, reduce the IL-17, TNF-α, and IL-6 levels in peripheral blood, promote the p-mTOR expression, and inhibit the expression of autophagy-related proteins in smoke-induced COPD mice. Conclusion. The number and alpha diversity of gut microbiota were decreased in patients with smoking-related COPD, accompanied by decreased abundance of Akkermansia muciniphila, and altered retinol metabolism function. Gut Akkermansia muciniphila ameliorated lung injury in smoke-induced COPD mice by inflammation and autophagy.

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“…This indicates impairment of cholesterol synthesis, uptake and efflux in the infected cells. However, RA treatments reverses this phenomenon, leading to increased cellular cholesterol and reduced parasite burden ( Prakash and Rai, 2022 ).…”

Section: Terpenic Compounds With Anti- Leishmania ...mentioning

confidence: 99%

Exploring the leishmanicidal potential of terpenoids: a comprehensive review on mechanisms of cell death

Rodrigues,

Carloto,

Gonçalves

et al. 2023

Front. Cell. Infect. Microbiol.

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Leishmaniasis is a neglected tropical disease with a wide spectrum of clinical manifestations, ranging from visceral to cutaneous, with millions of new cases and thousands of deaths reported each year. The species of Leishmania and the immune response of the host determine the severity of the disease. Leishmaniasis remains challenging to diagnose and treat, and there is no vaccine available. Several studies have been conducted on the use of herbal medicines for the treatment of leishmaniasis. Natural products can provide an inexhaustible source of chemical diversity with therapeutic potential. Terpenes are a class of natural products derived from a single isoprene unit, a five-carbon compound that forms the basic structure of isoprenoids. This review focuses on the most important and recent advances in the treatment of parasites of the genus Leishmania with different subclasses of terpenes. Several mechanisms have been proposed in the literature, including increased oxidative stress, immunomodulatory role, and induction of different types of parasite cell death. However, this information needs to be brought together to provide an overview of how these compounds can be used as therapeutic tools for drug development and as a successful adjuvant strategy against Leishmania sp.

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Retinoic Acid Increases Cellular Cholesterol in Leishmania donovani-Infected Macrophages in an mTOR-Independent Manner

Cited by 6 publications

References 23 publications

The impact of cholesteryl ester transfer protein on the progression of cutaneous leishmaniasis

The impact of cholesteryl ester transfer protein on the progression of cutaneous leishmaniasis

Akkermansia muciniphila Ameliorates Lung Injury in Smoke-Induced COPD Mice by IL-17 and Autophagy

Exploring the leishmanicidal potential of terpenoids: a comprehensive review on mechanisms of cell death

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