| Project/Area Number |
17K10042
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Infectious disease medicine
|
|---|
| Research Institution | Tokyo Medical University (2019)
National Institute of Infectious Diseases (2017-2018) |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | 肺炎球菌 / マクロファージ / オートファジー / CCL2 / 鼻咽頭クリアランス / 感染症 / 内科 |
|---|
| Outline of Final Research Achievements |
Pretreatment of macrophages with an autophagy inhibitor significantly reduced Ccl2 mRNA expression in the pneumococcal MOI 100-exposed group. Next, when Western blot was performed by stimulating J774 cells with Streptococcus pneumoniae, ATG5 and LC3 were detected, and the detection intensity was weakened by pretreatment with wortmannin. In fluorescent staining with anti-LC3 antibody, LC3 expression level increased by pneumococcal inoculation, and LC3 expression level decreased by wortmannin pretreatment. Observation with a transmission electron microscope confirmed the formation of a bilayer membrane structure that is considered to be an autophagosome that incorporated pneumococcal cells.
This study suggests that autophagy may be involved in the immune response to pneumococci by macrophages in terms of both phagocytosis and inflammatory response.
|
| Academic Significance and Societal Importance of the Research Achievements |
肺炎球菌感染、特に鼻咽頭クリアランスにおける宿主免疫応答が十分解明されておらず、また鼻咽頭クリアランスに着目した予防戦略もこれまでに認められていない。今回の研究成果は肺炎球菌に対するマクロファージ依存性防御機構、いわゆる自然免疫活性化による感染症防御法の新知見をオートファジーとの関連から明らかにしたものである。鼻粘膜局所におけるマクロファージのオートファジー活性化に基づくクリアランス機構の亢進による新たな肺炎球菌予防法を提案するものであり、将来的な臨床応用と社会福祉への貢献も可能であると考える。
|
