| RRC ID |
4653
|
| 著者 |
Yamasaki S, Matsumoto M, Takeuchi O, Matsuzawa T, Ishikawa E, Sakuma M, Tateno H, Uno J, Hirabayashi J, Mikami Y, Takeda K, Akira S, Saito T.
|
| タイトル |
C-type lectin Mincle is an activating receptor for pathogenic fungus, Malassezia.
|
| ジャーナル |
Proc Natl Acad Sci U S A
|
| 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.
|
| 巻・号 |
106(6)
|
| ページ |
1897-902
|
| 公開日 |
2009-2-10
|
| DOI |
10.1073/pnas.0805177106
|
| PII |
0805177106
|
| PMID |
19171887
|
| PMC |
PMC2644135
|
| MeSH |
Animals
Binding Sites
Cytokines / biosynthesis
Lectins, C-Type / deficiency
Lectins, C-Type / immunology
Lectins, C-Type / physiology*
Ligands
Macrophages / immunology
Macrophages / microbiology
Malassezia / pathogenicity*
Mannose / metabolism
Membrane Proteins / deficiency
Membrane Proteins / immunology
Membrane Proteins / physiology*
Mice
Mice, Knockout
Protein Array Analysis
|
| IF |
9.412
|
| 引用数 |
255
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 病原微生物 |
IFM 4802
IFM 4826
IFM 5218
IFM 5763
IFM 5787
IFM 5800
IFM 5807
IFM 40009
IFM 40022
IFM 40059
IFM 40066
IFM 40872
IFM 41134
IFM 41450
IFM 42197
IFM 45995
IFM 46839
IFM 46991
IFM 47439
IFM 47450
IFM 48429
IFM 48551
IFM 48586
IFM 48587
IFM 48588
IFM 48611
IFM 49824
IFM 49887
IFM 50261
IFM 51754
IFM 51940
IFM 51965
IFM 51970
IFM 52635
IFM 52993
IFM 53376
IFM 53930
IFM 53969
IFM 54222
IFM 54306
IFM 54308
IFM 54309
IFM 54310
IFM 54349
IFM 54350
IFM 54366
IFM 55047
IFM 55052 |
