| Project/Area Number |
26460523
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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 |
Bacteriology (including mycology)
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肺炎球菌 / リステリア / インフラマソーム / NLRP3 / ASC / STAT6 / IL-18 / IL-10 / 自然免疫 / 感染防御 / AIM2 / 気道粘膜 |
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| Outline of Final Research Achievements |
The aim of this study is to elucidate the roles for inflammasomes in infection with L. monocytogenes and S. pneumoniae, for the purpose of understanding pathological mechanism mediated by host-pathogen interactions. We found that the inflammasome adaptor ASC exacerbates lethal listeriosis by mediating IL-18 production, which leads to NK cell-dependent production of the immunosuppressive cytokine IL-10. It was also found that during pneumococcal pneumoniae, ASC sustains STAT6 activation in airway epithelial cells in an inflammasome-independent manner, thereby inhibiting the down-regulation of mucosal defense genes contributing to host defense against the pathogen. In addition, we reported that pneumolysin, a virulence factor of S. pneumoniae, plays a critical role in the production of IL-1α, which has been demonstrated as a mediator of lung inflammation, in response to this bacterium. The IL-1α production was dependent on calcium ions influx and calpain, but not the inflammasome.
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