Cutting edge: mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate

Hanne Schoenen, 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

Research output: Contribution to journalArticle

317 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2756-2760
Number of pages5
JournalThe Journal of Immunology
Volume184
Issue number6
Early online date17 Feb 2010
DOIs
Publication statusPublished - 15 Mar 2010

    Fingerprint

Cite this

Schoenen, H., Bodendorfer, B., Hitchens, K., Manzanero, S., Werninghaus, K., Nimmerjahn, F., Agger, E. M., Stenger, S., Andersen, P., Ruland, J., Brown, G. D., Wells, C., & Lang, R. (2010). Cutting edge: mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate. The Journal of Immunology, 184(6), 2756-2760. https://doi.org/10.4049/jimmunol.0904013