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

Hanne Schoenen | Zendy; Barbara Bodendorfer | Zendy; Kelly Hitchens | Zendy; Silvia Manzanero | Zendy; Kerstin Werninghaus | Zendy; Falk Nimmerjahn | Zendy; Else Marie Agger | Zendy; Steffen Stenger | Zendy; Peter Andersen | Zendy; Jürgen Ruland | Zendy; Gordon D. Brown | Zendy; Christine A. Wells | Zendy; Roland Lang | Zendy

Open Access

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

Author(s) -

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

Publication year - 2010

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.0904013

Subject(s) - syk , chemistry , innate immune system , pattern recognition receptor , mycobacterium bovis , microbiology and biotechnology , immune system , biology , immunology , signal transduction , mycobacterium tuberculosis , medicine , tyrosine kinase , tuberculosis , pathology

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.

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