| Project/Area Number |
17K10014
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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 |
Infectious disease medicine
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| Research Institution | Teikyo University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | マラリア / エクソソーム / HDL / 血小板 / CD36 / CD41 / エンドサイトーシス |
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| Outline of Final Research Achievements |
Malaria parasites cannot multiply in host erythrocytes without cholesterol because they lack complete sterol biosynthesis systems. This suggests parasitized red blood cells (pRBCs) need to capture host sterols, but its mechanism remains unknown. Here we identified a novel high-density lipoprotein (HDL)-delivery pathway operating in blood-stage Plasmodium. In parasitized mouse plasma, exosomes positive for scavenger receptor CD36 and platelet-specific CD41 increased. These CDs were detected in pRBCs and internal parasites. A low molecular antagonist for scavenger receptors, BLT-1, blocked HDL uptake to pRBCs and suppressed Plasmodium growth in vitro. Furthermore, platelet-derived exosomes were internalized in pRBCs. Thus, we presume CD36 is delivered to
malaria parasites from platelets by exosomes, which enables parasites to steal HDL for cholesterol supply.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、マラリア原虫が増殖に必要な脂質と脂質受容体を共に宿主に依存しており、その脂質受容体を得るために、宿主血小板を活性化して脂質受容体含有エクソソームを放出させているという、生物学的に極めて興味深い現象を明らかにした。この過程はマラリア原虫のいわばアキレス腱であり、治療薬の有力な標的候補でもある。アルテミシニン耐性熱帯熱マラリア原虫株が出現している現在、新しいクラスの抗マラリア薬開発は喫緊の課題であり、本研究をさらに創薬研究に発展させているところである。
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