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

Fadhil Ahsan, Jeroen Maertzdorf, Ute Guhlich-Bornhof, Stefan H.E. Kaufmann, Pedro Moura-Alves

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


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.

Original languageEnglish
Article number1520
JournalScientific Reports
Issue number1
Publication statusPublished - 1 Dec 2018
Externally publishedYes


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