C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia

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

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    270 Citations (Scopus)

    Abstract

    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 cytokine/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.

    Original languageEnglish
    Pages (from-to)1897-1902
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume106
    Issue number6
    DOIs
    Publication statusPublished - Feb 10 2009

    All Science Journal Classification (ASJC) codes

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    Yamasaki, S., Matsumoto, M., Takeuchi, O., Matsuzawa, T., Ishikawa, E., Sakuma, M., Tateno, H., Uno, J., Hirabayashi, J., Mikami, Y., Takeda, K., Akira, S., & Saito, T. (2009). C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia. Proceedings of the National Academy of Sciences of the United States of America, 106(6), 1897-1902. https://doi.org/10.1073/pnas.0805177106