S.flexneri effector OspI controls the accumulation of gamma-delta T cells to prevent epithelial cell death

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K07083
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Osaka University (2018-2019); The University of Tokyo (2016-2017)
• Principal Investigator: Sanada Takahito 大阪大学, 微生物病研究所, 特任研究員(常勤) (00569957)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 赤痢菌 / 炎症 / 病原細菌 / 細胞死

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.

Free Research Field

微生物学

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。