| Project/Area Number |
16K07083
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Osaka University (2018-2019)
The University of Tokyo (2016-2017) |
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Principal Investigator |
Sanada Takahito 大阪大学, 微生物病研究所, 特任研究員(常勤) (00569957)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 赤痢菌 / 炎症 / 病原細菌 / 細胞死 / 動物感染モデル / γδT細胞 / Fas / NF-κB / TRAF6 / ３型分泌タンパク質 / アポトーシス / 3型分泌機構 / NF-kB / 動物モデル / 宿主免疫応答 / III型分泌タンパク質 / OspI / 炎症抑制エフェクター / 細菌 / 感染症 / 病原性 / 細菌感染動物モデル |
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| Outline of Final Research Achievements |
To elucidate the physiological roles of OspI in vivo, we performed animal infection model to discern the physiological role of OspI. As expected from our previous study, Guenia pig and mice infected with ΔospI exhibited increased production of proinflammatory cytokines and chemokine, thereby demonstrating the negative regulatory role of OspI in vivo. In addition, the analysis of mice infected with ΔospI led us to identify previously unknown function of OspI as negative regulator of γδ T cell-mediated epithelial cell death. We found that γδ T cells exhibited a cytotoxic activity against epithelial cells infected with Shigella though Fas―FasL pathway, which could be avoided by OspI. Furthermore, OspI downregulated Fas induction in epithelial cells after Shigella infection. Together, the results of our study provide the first evidence supporting the negative regulatory role of OspI in host immune response.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、従来の通常の病原細菌感染実験では見落としていた 新たな炎症像解析を、抑制性エフェクター欠損株と野生株の感染による個体レベルでの比較解析 によって明らかにできる点が独創的である。実験動物の視点からは、複数のげっ歯類感染モデル の実績がある赤痢菌を用いることで、動物モデル間での病原体感染時宿主応答の比較も可能となる点が特色である。
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