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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >C-type Lectin Mincle Is An Activating Receptor For Pathogenic Fungus, Malassezia
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C-type Lectin Mincle Is An Activating Receptor For Pathogenic Fungus, Malassezia

机译：C型凝集素微粒是致病性真菌，马拉色菌的激活受体。

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摘要

Mincle (also called as Clec4e and Clecsf9) is a C-type lectin receptor expressed in activated phagocytes. Recently, we have demonstrated that Mincle is an FcRγ-associated activating receptor that senses damaged cells. To search an exogenous ligand(s), we screened pathogenic fungi using cell line expressing Mincle, FcRγ, and NFAT-GFP reporter. We found that Mincle specifically recognizes the Malassezia species among 50 different fungal species tested. Malassezia is a pathogenic fungus that causes skin diseases, such as tinea versicolor and atopic dermatitis, and fatal sepsis. However, the specific receptor on host cells has not been identified. Mutation of the putative mannose-binding motif within C-type lectin domain of Mincle abrogated Malassezia recognition. Analyses of glycoconjugate microarray revealed that Mincle selectively binds to α-mannose but not mannan. Thus, Mincle may recognize specific geometry of α-mannosyl residues on Malassezia species and use this to distinguish them from other fungi. Malassezia activated macrophages to produce inflammatory cytokines/ chemokines. To elucidate the physiological function of Mincle, Mincle-deficient mice were established. Malassezia-induced cyto-kine/chemokine production by macrophages from Mincle~(-/-) mice was significantly impaired. In vivo inflammatory responses against Malassezia was also impaired in Mincle~(-/-) mice. These results indicate that Mincle is the first specific receptor for Malassezia species to be reported and plays a crucial role in immune responses to this fungus.
机译：Mincle（也称为Clec4e和Clecsf9）是在活化的吞噬细胞中表达的C型凝集素受体。最近，我们证明了Mincle是一种与FcRγ相关的激活受体，可感知受损细胞。为了搜索外源配体，我们使用表达Mincle，FcRγ和NFAT-GFP报告基因的细胞系筛选了致病真菌。我们发现Mincle专门识别了50种不同的真菌物种中的Malassezia物种。马拉色菌病是一种引起皮肤疾病的致病性真菌，例如普通癣和特应性皮炎以及致命性败血症。但是，尚未鉴定宿主细胞上的特异性受体。 Mincle的C型凝集素结构域内推定的甘露糖结合基序的突变消除了马拉色菌的识别。糖缀合物微阵列的分析显示，Mincle选择性结合α-甘露糖，但不结合甘露聚糖。因此，Mincle可以识别马拉色菌属物种上的α-甘露糖残基的特定几何形状，并以此将它们与其他真菌区分开。马拉色菌激活巨噬细胞以产生炎性细胞因子/趋化因子。为了阐明Mincle的生理功能，建立了Mincle缺陷小鼠。 Mincle-（-/-）小鼠巨噬细胞引起的马拉色菌诱导的细胞因子/趋化因子的产生显着受损。在Mincle-（-/-）小鼠中，针对马拉色菌的体内炎症反应也被削弱。这些结果表明，Mincle是马拉色菌物种的第一个特异性受体，在对该真菌的免疫反应中起着至关重要的作用。

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  • 作者

    Sho Yamasaki; Makoto Matsumoto; Osamu Takeuchi; Tetsuhiro Matsuzawa; Eri Ishikawa; Machie Sakuma; Hiroaki Tateno; J.un Uno; Jun Hirabayashi; Yuzuru Mikami; Kiyoshi Takeda; Shizuo Akira; Takashi Saito;

  • 作者单位

    Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan;

    Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan;

    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan Laboratory of Host Defence, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan;

    Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan;

    Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan;

    Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan;

    Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Ibaraki 305-8568, Japan;

    Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan;

    Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Ibaraki 305-8568, Japan;

    Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan;

    Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan Laboratory of Mucosal Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan;

    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan Laboratory of Host Defence, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan;

    Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan Laboratory of Cell Signaling, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    itam; macrophages; signal transduction;

    机译：Itam;巨噬细胞;信号转导;

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