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

323 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 Dive into the research topics of 'Cutting edge: mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate'. Together they form a unique 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