title: C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia.
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 FcRgamma-associated activating receptor that senses damaged cells. To search an exogenous ligand(s), we screened pathogenic fungi using cell line expressing Mincle, FcRgamma, 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 alpha-mannose but not mannan. Thus, Mincle may recognize specific geometry of alpha-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.
authors.affiliation: Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan. sho@rcai.riken.jp
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Matsuzawa
authors.forename: Eri
authors.initials: E
authors.lastname: Ishikawa
authors.forename: Machie
authors.initials: M
authors.lastname: Sakuma
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tateno
authors.forename: Jun
authors.initials: J
authors.lastname: Uno
authors.forename: Jun
authors.initials: J
authors.lastname: Hirabayashi
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Mikami
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
mesh_terms: D000818:Animals; D001665:Binding Sites; D016207:Cytokines / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D008024:Ligands; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008290:Malassezia / Q000472:pathogenicity*; D008358:Mannose / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D040081:Protein Array Analysis
chemical_list: C113583:Clecsf8 protein, mouse; D016207:Cytokines; D037181:Lectins, C-Type; D008024:Ligands; D008565:Membrane Proteins; D008358:Mannose