Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan.
Cell Host Microbe. 2013 Apr 17;13(4):477-88. doi: 10.1016/j.chom.2013.03.008.
Various C-type lectin receptors (CLRs), including Mincle and Dectin-2, function as pattern recognition receptors and play a central role in immunity to fungal pathogens. However, the precise structures of the CLR ligands in various pathogenic fungi have yet to be completely defined. Here we report that Malassezia, an opportunistic skin fungal pathogen, is cooperatively recognized by Mincle and Dectin-2 through distinct ligands. Solvent-based fractionation revealed that Mincle and Dectin-2 recognize lipophilic and hydrophilic components of Malassezia, respectively. Mass spectrometry and nuclear magnetic resonance (NMR) revealed glyceroglycolipid and unique mannosyl fatty acids linked to mannitol as two Mincle ligands. An O-linked mannobiose-rich glycoprotein was identified as a Malassezia ligand for Dectin-2. Cytokine production in response to the Mincle ligands and the Dectin-2 ligand was abrogated in Mincle(-/-) and Dectin-2(-/-) dendritic cells, respectively. These results demonstrate that Mincle and Dectin-2 recognize distinct ligands in Malassezia to induce host immune responses.
各种 C 型凝集素受体（CLRs），包括 Mincle 和 Dectin-2，作为模式识别受体发挥作用，在真菌病原体的免疫中发挥核心作用。然而，各种致病性真菌中 CLR 配体的确切结构尚未完全定义。在这里，我们报告说，马拉色菌是一种机会性皮肤真菌病原体，通过不同的配体被 Mincle 和 Dectin-2 共同识别。基于溶剂的分馏表明，Mincle 和 Dectin-2 分别识别马拉色菌的亲脂性和亲水性成分。质谱和核磁共振（NMR）揭示了甘油糖脂和与甘露醇相连的独特甘露脂肪酸是两种 Mincle 配体。一种 O 连接的甘露二糖丰富的糖蛋白被鉴定为 Dectin-2 的马拉色菌配体。对 Mincle 配体和 Dectin-2 配体的细胞因子产生反应在 Mincle(-/-)和 Dectin-2(-/-)树突状细胞中分别被阻断。这些结果表明，Mincle 和 Dectin-2 识别马拉色菌中的不同配体以诱导宿主免疫反应。
