Cutting Edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate
Author(s)
Schoenen, Hanne
Bodendorfer, Barbara
Hitchens, Kelly
Manzanero Alonso, Silvia
Werninghaus, Kerstin
Nimmerjahn, Falk
Agger, Else Marie
Stenger, Steffen
Andersen, Peter
Ruland, Jurgen
D. Brown, Gordon
Wells, Christine
Lang, Roland
Year published
2010
Metadata
Show full item recordAbstract
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 FcRg was essential for macrophage activation and Th17 adjuvanticity. The FcRg-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 ...
View more >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 FcRg was essential for macrophage activation and Th17 adjuvanticity. The FcRg-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 FcRg were impaired in the inflammatory response to Mycobacterium bovis bacillus Calmette- Gue䲩n. These results establish that Mincle is a key receptor for the mycobacterial cord factor and controls the Th1/Th17 adjuvanticity of TDM and TDB. The Journal of Immunology, 2010, 184: 2756-2760.
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View more >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 FcRg was essential for macrophage activation and Th17 adjuvanticity. The FcRg-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 FcRg were impaired in the inflammatory response to Mycobacterium bovis bacillus Calmette- Gue䲩n. These results establish that Mincle is a key receptor for the mycobacterial cord factor and controls the Th1/Th17 adjuvanticity of TDM and TDB. The Journal of Immunology, 2010, 184: 2756-2760.
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Journal Title
Journal of Immunology
Volume
184
Issue
6
Copyright Statement
Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
Subject
Immunology not elsewhere classified
Immunology