Portal de Periódicos da CAPES

Cutting Edge: Mincle Is Essential for Recognition and Adjuvanticity of the Mycobacterial Cord Factor and its Synthetic Analog Trehalose-Dibehenate

2010; American Association of Immunologists; Volume: 184; Issue: 6 Linguagem: Inglês

10.4049/jimmunol.0904013

1550-6606

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 A. Wells, Roland Lang,

Immunotherapy and Immune Responses

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 FcRγ was essential for macrophage activation and Th17 adjuvanticity. The FcRγ-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 FcRγ 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.