| Project/Area Number |
17K15677
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Parasitology (including sanitary zoology)
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| Research Institution | Osaka University |
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Principal Investigator |
BANDO HIRONORI 大阪大学, 微生物病研究所, 特任研究員(常勤) (60724367)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | トキソプラズマ / ヒト / 病原因子 / IDO1 / TgIST / GRA15 / Toxoplasma gondii / human |
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| Outline of Final Research Achievements |
Toxoplasma is an important intracellular pathogen that causes lethal toxoplasmosis in humans and animals. Interferon-γ (IFN-γ) is critical for anti-T. gondii responses in both human and mice. Recent studies use the mouse as a model organism and show the relation between host immunity and T. gondii virulence in mice. On the other hands, the relation in human is not completely clear. Therefore, we focus on T. gondii virulence strategy to resist IFN-γ-induced anti-T. gondii responses in human. At first, we showed that IFN-γ-induced tryptophan degradation by indole-2,3-dioxygenase plays an important role in the IFN-γ-induced inhibition of T. gondii in various human cell types. Next, we showed the role of T. gondii virulence factor TgIST or TgGRA15 to suppress IFN-γ-dependent immunity. Thus, we clear the interaction between T. gondii and host immune response in human cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で私たちは、ヒトの細胞で抗トキソプラズマ免疫反応に重要な宿主分子としてIDO1を同定し、また、実際にトキソプラズマはヒトの細胞では、IDO1を抑制する病原因子を利用していることも示しました。この研究成果から、IDO1を新たな標的として、その機能を高めることによって新規の治療・予防戦略を提供できることが期待されます。さらに本研究では、トキソプラズマがIDO1の機能を阻害するために病原因子を利用して産生誘導しているNOの産生を阻害すると、トキソプラズマによる免疫抑制作用を回避できることも示しました。この成果から、NO阻害剤がトキソプラズマ症の新規の治療戦略となることが期待されます。
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