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

Schoenen, H. et al. (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), pp. 2756-2760. (doi: 10.4049/jimmunol.0904013)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Wells, Dr Christine
• Authors: 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.A., and Lang, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Group: Wells
• Journal Name: Journal of Immunology
• Journal Abbr.: J. Immunol.
• ISSN: 0022-1767
• ISSN (Online): 1550-6606