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标题：IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis
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作者：Fadhil Ahsan ; Jeroen Maertzdorf ; Ute Guhlich-Bornhof 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：1520
DOI：10.1038/s41598-018-19476-x
语种：English
出版社：Springer Nature
摘要：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.