| Literature DB >> 20164423 |
Hanne Schoenen1, Barbara Bodendorfer, Kelly Hitchens, Silvia Manzanero, Kerstin Werninghaus, Falk Nimmerjahn, Else Marie Agger, Steffen Stenger, Peter Andersen, Jürgen Ruland, Gordon D Brown, Christine Wells, Roland Lang.
Abstract
The mycobacterial cord factor trehalose-6,6-dimycolate (TDM) and its synthetic analog trehalose-6,6-dibehenate (TDB) are potent adjuvants for Th1/Th17 vaccination that activate Syk-Card9 signaling in APCs. In this study, we have further investigated the molecular mechanism of innate immune activation by TDM and TDB. The Syk-coupling adapter protein FcRgamma was essential for macrophage activation and Th17 adjuvanticity. The FcRgamma-associated C-type lectin receptor Mincle was expressed in macrophages and upregulated by TDM and TDB. Recombinant Mincle-Fc fusion protein specifically bound to the glycolipids. Genetic ablation of Mincle abolished TDM/TDB-induced macrophage activation and induction of T cell immune responses to a tuberculosis subunit vaccine. Macrophages lacking Mincle or FcRgamma were impaired in the inflammatory response to Mycobacterium bovis bacillus Calmette-Guérin. These results establish that Mincle is a key receptor for the mycobacterial cord factor and controls the Th1/Th17 adjuvanticity of TDM and TDB.Entities:
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Year: 2010 PMID： 20164423 PMCID： PMC3442336 DOI： 10.4049/jimmunol.0904013
Source DB: PubMed Journal: J Immunol ISSN： 0022-1767 Impact factor: 5.422