| Project/Area Number |
12670261
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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 | University of the Ryukyus |
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Principal Investigator |
KAWAKAMI Kazuyoshi University of the Ryukyus, Faculty of Medicine, Associate professor, 医学部, 助教授 (10253973)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Fungal infection / Cryptococcus / Penicillium marneffei / Innate immunity / NKT cells / γδT cells / オステオポンチン / エイズ / 日和見真菌感染症 / NK細胞 / IFN-_γ / IL-18 / IL-12 / IFN-gamma |
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| Research Abstract |
We have investigated the host defense mechanism against Cryptococcus neoformans infection using a mouse model to clarify the molecular mechanisms of opportunistic fungal infection complicated in AIDS. In this study, we evaluated the roles of innate immune lymphocytes, such as NK NKT and γδ T cells. NK and NKT cells accumulated in lung and regional lymphmode in a MCP-1-dependent manner after cryptococcal infection, while the accumulation of γδ T cells was not dependent of this chemokine. NKT cells were found to play an important role in the development of Th1-mediated host protection from this infection using mice genetically lacking Vα14 NKT cells. In contrast, γδ T cells were suggested to negatively regulate these responses, because the infection was improved in mice depleted of these cells by administration of ant-γδ TCR mAb. Further investigations are now under way. On the other hand, we also demonstrated in an in-vitro study using peripheral blood mononuclear cells the involvement of osteopontin in the IL-12-induced Th1 responses in infection with Penicillium marneffei, a major opportunistic fungal pathogen in AIDS patients in Southeast Asia. In the present study, we have approached the process reaching from innate to acquired immune responses during fungal infection, which may provide a basic implication in constructing the strategies for prevention and treatment against AIDS-related infection caused by these pathogens.
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