Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate.
Schoenen H, Bodendorfer B, Hitchens K, Manzanero S, Werninghaus K, Nimmerjahn F, Agger EM, Stenger S, Andersen P, Ruland J, Brown GD, Wells C, Lang R (2010)
Publication Type: Journal article
Publication year: 2010
Journal
Publisher: American Association of Immunologists
Book Volume: 184
Pages Range: 2756-60
Journal Issue: 6
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.
Authors with CRIS profile
Falk Nimmerjahn
Lehrstuhl für Genetik
Roland Lang
Professur für Angeborene Immunität und Pathogenerkennung
Involved external institutions
Griffith University
Australia (AU)
Statens Serum Institut
Denmark (DK)
Technische Universität München (TUM)
Germany (DE)
University of Aberdeen
United Kingdom (GB)
Universitätsklinikum Ulm
Germany (DE)
Australia (AU)
Statens Serum Institut
Denmark (DK)
Technische Universität München (TUM)
Germany (DE)
University of Aberdeen
United Kingdom (GB)
Universitätsklinikum Ulm
Germany (DE)
How to cite
APA:
Schoenen, H., Bodendorfer, B., Hitchens, K., Manzanero, S., Werninghaus, K., Nimmerjahn, F.,... Lang, R. (2010). Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. Journal of Immunology, 184(6), 2756-60. https://dx.doi.org/10.4049/jimmunol.0904013
MLA:
Schoenen, Hanne, et al. "Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate." Journal of Immunology 184.6 (2010): 2756-60.
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