In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2018-01-24)
Kurzfassung:
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 .
Materialart:
Online-Ressource
ISSN:
2045-2322
DOI:
10.1038/s41598-018-19476-x
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2018
ZDB Id:
2615211-3
