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.
NCBI PubMed ID: 23601109Publication DOI: 10.1016/j.chom.2013.03.008Journal NLM ID: 101302316Publisher: Cambridge, MA: Cell Press
Correspondence: Miyamoto T
; Yamasaki S
Institutions: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan, Department of Infection and Host Defense, Tohoku Pharmaceutical University, Sendai, Japan, Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan, Research Center for Advanced Immunology, Kyushu University, Fukuoka, Japan, Department of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan, Department of Bio-resources, Medical Mycology Research Center, Chiba University, Chiba, Japan, Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Saitama, Japan, Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
Methods: 13C NMR, 1H NMR, FAB-MS, GC-MS, SDS-PAGE, TLC, ELISA, composition analysis, alkaline hydrolysis, reduction with NaBD4, acetylation, HPTLC, TOCSY, methylation analysis, reduction with NaBH4, ESI-TOF-MS, HMBC, COSY, NOESY, HSQC, HCl hydrolysis, TFA hydrolysis, absolute configuration determination
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