TY - JOUR
T1 - IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis
AU - Ahsan, Fadhil
AU - Maertzdorf, Jeroen
AU - Guhlich-Bornhof, Ute
AU - Kaufmann, Stefan H.E.
AU - Moura-Alves, Pedro
N1 - Funding Information:
This work was supported by the Max Planck Society to S.H.E.K. We thank the Core Facility Microscopy at MPIIB Berlin for the fluorescence imaging support. Special thanks to Teresa Domaszewska and the Microarray Core Facility for microarray analysis. S.H.E.K. acknowledges additional support from the grant from EU FP7 project “ADITEC” (HEALTH-F4-2011-280873). This work was supported by the Max Planck Society and the EU FP7 project ADITEC (HEALTH-F4-2011-280873).
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85041098857&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-19476-x
DO - 10.1038/s41598-018-19476-x
M3 - Article
C2 - 29367626
AN - SCOPUS:85041098857
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 1520
ER -
