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

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

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  • Media type: E-Article
  • Title: Cutting Edge: Mincle Is Essential for Recognition and Adjuvanticity of the Mycobacterial Cord Factor and its Synthetic Analog Trehalose-Dibehenate
  • Contributor: Schoenen, Hanne; Bodendorfer, Barbara; Hitchens, Kelly; Manzanero, Silvia; Werninghaus, Kerstin; Nimmerjahn, Falk; Agger, Else Marie; Stenger, Steffen; Andersen, Peter; Ruland, Jürgen; Brown, Gordon D.; Wells, Christine; Lang, Roland
  • imprint: The American Association of Immunologists, 2010
  • Published in: The Journal of Immunology
  • Language: English
  • DOI: 10.4049/jimmunol.0904013
  • ISSN: 0022-1767; 1550-6606
  • Keywords: Immunology ; Immunology and Allergy
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:p>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.</jats:p>
  • Access State: Open Access