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IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) is a life-threatening pathogen in humans. Bacterial infection of macrophages usually triggers strong innate immune mechanisms, including IL-1 cytokine secretion. The newer member of the IL-1 family, IL-36, was recently shown to be involved in cellular defense against...

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Autores principales: Ahsan, Fadhil, Maertzdorf, Jeroen, Guhlich-Bornhof, Ute, Kaufmann, Stefan H. E., Moura-Alves, Pedro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784124/
https://www.ncbi.nlm.nih.gov/pubmed/29367626
http://dx.doi.org/10.1038/s41598-018-19476-x
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author Ahsan, Fadhil
Maertzdorf, Jeroen
Guhlich-Bornhof, Ute
Kaufmann, Stefan H. E.
Moura-Alves, Pedro
author_facet Ahsan, Fadhil
Maertzdorf, Jeroen
Guhlich-Bornhof, Ute
Kaufmann, Stefan H. E.
Moura-Alves, Pedro
author_sort Ahsan, Fadhil
collection PubMed
description Mycobacterium tuberculosis (Mtb) is a life-threatening pathogen in humans. Bacterial infection of macrophages usually triggers strong innate immune mechanisms, including IL-1 cytokine secretion. The newer member of the IL-1 family, IL-36, was recently shown to be involved in cellular defense against Mtb. To unveil the underlying mechanism of IL-36 induced antibacterial activity, we analyzed its role in the regulation of cholesterol metabolism, together with the involvement of Liver X Receptor (LXR) in this process. We report that, in Mtb-infected macrophages, IL-36 signaling modulates cholesterol biosynthesis and efflux via LXR. Moreover, IL-36 induces the expression of cholesterol-converting enzymes and the accumulation of LXR ligands, such as oxysterols. Ultimately, both IL-36 and LXR signaling play a role in the regulation of antimicrobial peptides expression and in Mtb growth restriction. These data provide novel evidence for the importance of IL-36 and cholesterol metabolism mediated by LXR in cellular host defense against Mtb.
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spelling pubmed-57841242018-02-07 IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis Ahsan, Fadhil Maertzdorf, Jeroen Guhlich-Bornhof, Ute Kaufmann, Stefan H. E. Moura-Alves, Pedro Sci Rep Article Mycobacterium tuberculosis (Mtb) is a life-threatening pathogen in humans. Bacterial infection of macrophages usually triggers strong innate immune mechanisms, including IL-1 cytokine secretion. The newer member of the IL-1 family, IL-36, was recently shown to be involved in cellular defense against Mtb. To unveil the underlying mechanism of IL-36 induced antibacterial activity, we analyzed its role in the regulation of cholesterol metabolism, together with the involvement of Liver X Receptor (LXR) in this process. We report that, in Mtb-infected macrophages, IL-36 signaling modulates cholesterol biosynthesis and efflux via LXR. Moreover, IL-36 induces the expression of cholesterol-converting enzymes and the accumulation of LXR ligands, such as oxysterols. Ultimately, both IL-36 and LXR signaling play a role in the regulation of antimicrobial peptides expression and in Mtb growth restriction. These data provide novel evidence for the importance of IL-36 and cholesterol metabolism mediated by LXR in cellular host defense against Mtb. Nature Publishing Group UK 2018-01-24 /pmc/articles/PMC5784124/ /pubmed/29367626 http://dx.doi.org/10.1038/s41598-018-19476-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ahsan, Fadhil
Maertzdorf, Jeroen
Guhlich-Bornhof, Ute
Kaufmann, Stefan H. E.
Moura-Alves, Pedro
IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis
title IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis
title_full IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis
title_fullStr IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis
title_full_unstemmed IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis
title_short IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis
title_sort il-36/lxr axis modulates cholesterol metabolism and immune defense to mycobacterium tuberculosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784124/
https://www.ncbi.nlm.nih.gov/pubmed/29367626
http://dx.doi.org/10.1038/s41598-018-19476-x
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