TY - JOUR
T1 - Identification of distinct ligands for the C-type lectin receptors mincle and dectin-2 in the pathogenic fungus Malassezia
AU - Ishikawa, Tetsuaki
AU - Itoh, Fumie
AU - Yoshida, Sayumi
AU - Saijo, Shinobu
AU - Matsuzawa, Tetsuhiro
AU - Gonoi, Tohru
AU - Saito, Takashi
AU - Okawa, Yoshio
AU - Shibata, Nobuyuki
AU - Miyamoto, Tomofumi
AU - Yamasaki, Sho
N1 - Funding Information:
We thank Y. Iwakura and S. Akira for providing mutant mice and Y. Nishi-Sanui for secretary assistance. This work was supported by Grant-in-Aid for Young Scientists (S), Funding Program for Next Generation World-Leading Researchers (NEXT Program), Ono Medical Research Foundation (S. Yamasaki), and Grant-in-Aid for JSPS (T.I.). This work was partly performed with the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University.
PY - 2013/4/17
Y1 - 2013/4/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84876354592&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876354592&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2013.03.008
DO - 10.1016/j.chom.2013.03.008
M3 - Article
C2 - 23601109
AN - SCOPUS:84876354592
SN - 1931-3128
VL - 13
SP - 477
EP - 488
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 4
ER -