Cutting Edge: Mincle Is Essential for Recognition and Adjuvanticity of the Mycobacterial Cord Factor and its Synthetic Analog Trehalose-Dibehenate
| Autor: | Silvia Manzanero, Peter Henrik Andersen, Gordon D. Brown, Kelly J Hitchens, Roland Lang, Hanne Schoenen, Barbara Bodendorfer, Falk Nimmerjahn, Else Marie Agger, Kerstin Werninghaus, Christine A. Wells, Steffen Stenger, Juergen Ruland |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
0303 health sciences
Cord factor Innate immune system T cell Immunology Biology Fusion protein 3. Good health Microbiology Trehalose dimycolate 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine.anatomical_structure Immune system chemistry C-type lectin Adjuvanticity medicine Immunology and Allergy 030304 developmental biology 030215 immunology |
| Zdroj: | The Journal of Immunology; Vol 184 The Journal of Immunology |
| ISSN: | 0022-1767 |
| DOI: | 10.4049/jimmunol.0904013 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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