Send to:

Choose Destination
See comment in PubMed Commons below
Cell Microbiol. 2010 Nov;12(11):1648-65. doi: 10.1111/j.1462-5822.2010.01497.x. Epub 2010 Jul 20.

Mycobacterial lipoprotein activates autophagy via TLR2/1/CD14 and a functional vitamin D receptor signalling.

Author information

  • 1Department of Microbiology, Chungnam National University School of Medicine, Daejeon, Korea.


In human monocytes, Toll-like receptor (TLR) 2/1 activation leads to vitamin D3-dependent antimycobacterial activities, but the molecular mechanisms by which TLR2/1 stimulation induces antimicrobial activities against mycobacteria remain unclear. Here we show that TLR2/1/CD14 stimulation by mycobacterial lipoprotein LpqH can robustly activate antibacterial autophagy through vitamin D receptor signalling activation and cathelicidin induction. We found that CCAAT/enhancer-binding protein (C/EBP)-β-dependent induction of 25-hydroxycholecalciferol-1α-hydroxylase (Cyp27b1) hydroxylase was critical for LpqH-induced cathelicidin expression and autophagy. In addition, increases in intracellular calcium following AMP-activated protein kinase (AMPK) activation played a crucial role in LpqH-induced autophagy. Moreover, AMPK-dependent p38 mitogen-activated protein kinase (MAPK) activation was required for LpqH-induced Cyp27b1 expression and autophagy activation. Collectively, these data suggest that TLR2/1/CD14-Ca(2+) -AMPK-p38 MAPK pathways contribute to C/EBP-β-dependent expression of Cyp27b1 and cathelicidin, which played an essential role in LpqH-induced autophagy. Furthermore, these results establish a previously uncharacterized signalling pathway of antimycobacterial host defence through a functional link of TLR2/1/CD14-dependent sensing to the induction of autophagy.

© 2010 Blackwell Publishing Ltd.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Write to the Help Desk