Journal article
IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis
- Abstract:
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 6.1MB, Terms of use)
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- Publisher copy:
- 10.1038/s41598-018-19476-x
Authors
- Publisher:
- Springer Nature
- Journal:
- Scientific Reports More from this journal
- Volume:
- 8
- Article number:
- 1520
- Publication date:
- 2018-01-24
- Acceptance date:
- 2017-12-27
- DOI:
- EISSN:
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2045-2322
- Pmid:
-
29367626
- Language:
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English
- Pubs id:
-
pubs:939832
- UUID:
-
uuid:69c88c8c-c42d-49fb-9b31-f2a2073ac8d7
- Local pid:
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pubs:939832
- Source identifiers:
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939832
- Deposit date:
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2018-11-09
Terms of use
- Copyright holder:
- Ahsan et al
- Copyright date:
- 2018
- Notes:
- © The Authors 2018. 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. Te 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/.
- Licence:
- CC Attribution (CC BY)
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