Journal article
Cutting Edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate
H Schoenen, B Bodendorfer, K Hitchens, S Manzanero, K Werninghaus, F Nimmerjahn, EM Agger, S Stenger, P Andersen, J Ruland, GD Brown, C Wells, R Lang
Journal of Immunology | Published : 2010
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 FcRγ was essential for macrophage activation and Th17 adjuvanticity. The FcRγ-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..
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Awarded by European Commission
Funding Acknowledgements
This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB796, TP B6 to R.L; SFB576 to J.R.; SFB643 and FOR832 to F.N.) and the European Union (FP6 TBVAC to E.M.A., P.A., and R.L., Contract Number LSHP-CT-2003-503367), a Max-Eder-Programm grant from Deutsche Krebshilfe (to J.R.), the Wellcome Trust (to G.D.B.), and The National Health and Medical Research Council, Australia (455947, 597452, and 481945 to C.W.).