| http://purl.uniprot.org/citations/26202982 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26202982 | http://www.w3.org/2000/01/rdf-schema#comment | "Trehalose-6,6-dimycolate (TDM), the mycobacterial cord factor, is an abundant cell wall glycolipid and major virulence factor of Mycobacterium tuberculosis. Its synthetic analog trehalose-6,6-dibehenate (TDB) is a new adjuvant currently in phase I clinical trials. In rodents, the C-type lectin receptors Mincle and Mcl bind TDB/TDM and activate macrophages and dendritic cells (DC) through the Syk-Card9 pathway. However, it is unknown whether these glycolipids activate human innate immune cells through the same mechanism. We performed in vitro analysis of TDB/TDM-stimulated primary human monocytes, macrophages, and DC; determined C-type lectin receptor expression; and tested the contribution of SYK, MINCLE, and MCL by small interfering RNA knockdown and genetic complementation. We observed a robust chemokine and cytokine release in response to TDB or TDM. MCSF-driven macrophages secreted higher levels of IL-8, IL-6, CCL3, CCL4, and CCL2 after stimulation with TDM, whereas DC responded more strongly to TDB and GM-CSF-driven macrophages were equally responsive to TDB and TDM. SYK kinase and the adaptor protein CARD9 were essential for glycolipid-induced IL-8 production. mRNA expression of MINCLE and MCL was high in monocytes and macrophages, with MINCLE and MCL proteins localized intracellularly under resting conditions. Small interfering RNA-mediated MINCLE or MCL knockdown caused on average reduced TDB- or TDM-induced IL-8 production. Conversely, retroviral expression in murine Mincle-deficient DC revealed that human MINCLE, but not MCL, was sufficient to confer responsiveness to TDB/TDM. Our study demonstrates that SYK-CARD9 signaling plays a key role in TDB/TDM-induced activation of innate immune cells in man as in mouse, likely by engagement of MINCLE."xsd:string |
| http://purl.uniprot.org/citations/26202982 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1500102"xsd:string |
| http://purl.uniprot.org/citations/26202982 | http://purl.uniprot.org/core/author | "Hofmann K."xsd:string |
| http://purl.uniprot.org/citations/26202982 | http://purl.uniprot.org/core/author | "Zimmermann S."xsd:string |
| http://purl.uniprot.org/citations/26202982 | http://purl.uniprot.org/core/author | "Lang R."xsd:string |
| http://purl.uniprot.org/citations/26202982 | http://purl.uniprot.org/core/author | "Jozefowski K."xsd:string |
| http://purl.uniprot.org/citations/26202982 | http://purl.uniprot.org/core/author | "Lepenies B."xsd:string |
| http://purl.uniprot.org/citations/26202982 | http://purl.uniprot.org/core/author | "Ostrop J."xsd:string |
| http://purl.uniprot.org/citations/26202982 | http://purl.uniprot.org/core/author | "Strasser E."xsd:string |
| http://purl.uniprot.org/citations/26202982 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26202982 | http://purl.uniprot.org/core/name | "J Immunol"xsd:string |
| http://purl.uniprot.org/citations/26202982 | http://purl.uniprot.org/core/pages | "2417-2428"xsd:string |
| http://purl.uniprot.org/citations/26202982 | http://purl.uniprot.org/core/title | "Contribution of MINCLE-SYK Signaling to Activation of Primary Human APCs by Mycobacterial Cord Factor and the Novel Adjuvant TDB."xsd:string |
| http://purl.uniprot.org/citations/26202982 | http://purl.uniprot.org/core/volume | "195"xsd:string |
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