| Project/Area Number |
18K09544
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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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| Review Section |
Basic Section 57020:Oral pathobiological science-related
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| Research Institution | Meikai University (2021)
Asahi University (2018-2020) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
岩橋 均 岐阜大学, 応用生物科学部, 教授 (60356540)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | オートファジー / LAP / 加齢 / 肺炎レンサ球菌 / 細菌感染症 / 肺炎球菌 / 肺炎 / 細菌感染 / 肺炎・誤嚥性肺炎 / 感染症 |
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| Outline of Final Research Achievements |
In this study, we investigated the relationship between Streptococcus pneumoniae and autophagy / LC3 associated phagocytosis (LAP) in macrophages. We found that
macrophages utilize LAP, rather than canonical autophagy,to both eliminate S. pneumoniae and modulate inflammation. Notably, compared to young macrophages,aged acrophages were deficient in LAP, resulting incompromised bacterial killing and enhanced proinflammatory responses. Thus, S. pneumoniae triggers LAP in macrophages, a process that controls both microbial numbers and tissue-damaging inflammation. Importantly, LAP diminishes with age and may contribute to the observed susceptibility of the elderly to many infectious diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
肺炎レンサ球菌に対する感受性は65歳以上の高齢者で著しく高くなり，高齢者人口の急増する日本や米国では肺炎レンサ球菌感染症による死亡が増加し問題となっている．本研究では, 高齢者に肺炎レンサ球菌感染症が好発するメカニズムについて明らかにすることを目的とした.
研究を遂行した結果, 加齢により肺炎レンサ球菌の誘導するオートファジー/LAPが減弱し, その結果, 肺炎レンサ球菌に対する分解・排除機構が破綻することを明らかにした. 得られた成果は, 高齢者における肺炎病態の発症・進展メカニズムに関与すると考えられる.
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