title: Identification of distinct ligands for the C-type lectin receptors Mincle and Dectin-2 in the pathogenic fungus Malassezia.
abstract: 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.
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Fumie
authors.initials: F
authors.lastname: Itoh
authors.forename: Sayumi
authors.initials: S
authors.lastname: Yoshida
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Matsuzawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Gonoi
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Okawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shibata
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005658:Fungi / Q000276:immunology* / Q000378:metabolism; D006017:Glycolipids / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008290:Malassezia / Q000276:immunology* / Q000378:metabolism; D008358:Mannose / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011975:Receptors, Mitogen / Q000276:immunology* / Q000378:metabolism
chemical_list: C113583:Clecsf8 protein, mouse; D016207:Cytokines; D006017:Glycolipids; D006023:Glycoproteins; D037181:Lectins, C-Type; D008024:Ligands; D008565:Membrane Proteins; D011975:Receptors, Mitogen; C445340:dectin-2, mouse; D008358:Mannose