1. C-type lectin Mincle is an activating receptor for pathogenic fungus,Malassezia
- Author
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Machie Sakuma, Hiroaki Tateno, Jun Uno, Yuzuru Mikami, Osamu Takeuchi, Tetsuhiro Matsuzawa, Shizuo Akira, Makoto Matsumoto, Takashi Saito, Jun Hirabayashi, Sho Yamasaki, Eri Ishikawa, and Kiyoshi Takeda
- Subjects
Chemokine ,Protein Array Analysis ,Ligands ,Microbiology ,Proinflammatory cytokine ,Mice ,Immune system ,C-type lectin ,medicine ,Animals ,Lectins, C-Type ,Receptor ,Mice, Knockout ,Binding Sites ,Malassezia ,Multidisciplinary ,integumentary system ,biology ,Macrophages ,Membrane Proteins ,Biological Sciences ,Pathogenic fungus ,biology.organism_classification ,medicine.disease ,Tinea versicolor ,Immunology ,biology.protein ,Cytokines ,Mannose - 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 theMalasseziaspecies among 50 different fungal species tested.Malasseziais 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 abrogatedMalasseziarecognition. 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 onMalasseziaspecies and use this to distinguish them from other fungi.Malasseziaactivated 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 againstMalasseziawas also impaired in Mincle−/−mice. These results indicate that Mincle is the first specific receptor forMalasseziaspecies to be reported and plays a crucial role in immune responses to this fungus.
- Published
- 2009