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...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2018
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| _version_ | 1826277120466223104 |
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| author | Ahsan, F Maertzdorf, J Guhlich-Bornhof, U Kaufmann, S Moura-Alves, P |
| author_facet | Ahsan, F Maertzdorf, J Guhlich-Bornhof, U Kaufmann, S Moura-Alves, P |
| author_sort | Ahsan, F |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-06T23:24:07Z |
| format | Journal article |
| id | oxford-uuid:69c88c8c-c42d-49fb-9b31-f2a2073ac8d7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:24:07Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:69c88c8c-c42d-49fb-9b31-f2a2073ac8d72022-03-26T18:53:12ZIL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:69c88c8c-c42d-49fb-9b31-f2a2073ac8d7EnglishSymplectic Elements at OxfordSpringer Nature2018Ahsan, FMaertzdorf, JGuhlich-Bornhof, UKaufmann, SMoura-Alves, PMycobacterium 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. |
| spellingShingle | Ahsan, F Maertzdorf, J Guhlich-Bornhof, U Kaufmann, S Moura-Alves, P 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 |
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