Activation of innate immune responses and its regulation by NKT cells and γδT cells in fungal infection
| Project/Area Number |
18590413
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Tohoku University |
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Principal Investigator |
KAWAKAMI Kazuyoshi Tohoku University, Tohoku University, Faculty of Medicine, Professor (10253973)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAGAWA Kiyotaka Tohoku University Graduate School of Agricultural Science, 大学院・農学研究科, Associate Professor (80361145)
MIYAZATO Akiko Tohoku University Hospital, 病院, Assistant Professor (50400370)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | fungus / Cryptococcus neoformans / Candida albicans / Penicillium marneffei / innate immunity / NKT cells / DNA / TLR9 / 真菌感染 / γδT細胞 / 樹状細胞 / CDId / 脂質抗原 / IFN一γ |
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| Research Abstract |
Fungi are opportunistic pathogens in hosts with impaired immune responses. Host eliminates the infected microorganisms by sensing them and developing the activation of innate and acquired immunity. During these processes, TLR and C-type lectin-like receptors play important roles and innate immune lymphocytes such as NKT cells and γδ T cells are activated.
In this study, we clarified the contribution of TLR2 and dectin-1, a (β-glucan receptor, in the recognition of Penicillium marneffei by dendritic cells (DC). We also found that the role of dectin-1 differed among fungi, as shown by its limited role in sensing Candida albicans and Cryptococcus neoformans. Furthermore, we found that DNA from C. albicans, C. neoformans, Aspergillus fumigates and Trichosporon spp. activated DC by inducing IL-12 production and CD40 expression and that these activities were mediated by a TLR9/MyD88/NF_κB-dependent signaling pathway in case of C. albicans and C. neoformans. DNA from these fungi trafficked into endosomal compartments and interacted with TLR9. This mechanism was likely to function in vivo because lung infection with a certain strain of C. neoformans was worsened in TLR9 gene-disrupted (KO) mice.
In other study, to address the mechanism of NKT cell-mediated host defense against C. neoformans infection, we tried to found a possible glycolipid antigen recognized by NKT cells in the lysates of this fungal pathogen and showed that bone marrow-derived DC pulsed with C. neoformans activated liver mononuclear cells (LMNC) containing much NKT cells by inducing IFN-γ production, which was strongly inhibited by neutralizing anti-CD 1d mAb or when DC from CDldKO mice or LMNC from Jα18KO mice were used. These results strongly supported the existence of glycolipid antigens in C. neoformans which activate NKT cells.
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Report
(3 results)
Research Products
(32 results)
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[Book] 内科学2006
Author(s)
川上和義、斎藤 厚
Publisher
医学書院
Description
「研究成果報告書概要(和文)」より
Related Report
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