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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Cutting Edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate
Journal of Immunology, Volume 184, No. 6, Year 2010
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Description
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. Copyright © 2010 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Schoenen, Hanne
Germany, Erlangen
Universitätsklinikum Erlangen
Hitchens, Kelly J.
Australia, Brisbane
Griffith University
Werninghaus, Kerstin
Germany, Erlangen
Universitätsklinikum Erlangen
Nimmerjahn, F.
Germany, Erlangen
Friedrich-alexander-universität Erlangen-nürnberg
Agger, Else Marie
Denmark, Copenhagen
Statens Serum Institut
Stenger, Steffen
Germany, Ulm
Universitätsklinikum Ulm
Andersen, Peter Lawætz
Denmark, Copenhagen
Statens Serum Institut
Ruland, Jürgen
Germany, Munich
Technische Universität München
Brown, Gordon D.A.
United Kingdom, Aberdeen
University of Aberdeen
Wells, Christine A.
Australia, Brisbane
Griffith University
Lang, Roland
Germany, Erlangen
Universitätsklinikum Erlangen
Statistics
Citations: 394
Authors: 11
Affiliations: 7
Identifiers
Doi:
10.4049/jimmunol.0904013
ISSN:
15506606
Research Areas
Genetics And Genomics