2021 Fiscal Year Final Research Report
The effect of LPS preconditioning on the lethal mlaria infection
| Project/Area Number |
19K07493
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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 49030:Experimental pathology-related
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| Research Institution | National Defense Medical College |
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Principal Investigator |
Ono Takeshi 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 国際感染症学, 助教 (20535182)
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| Co-Investigator(Kenkyū-buntansha) |
木下 学 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 免疫・微生物学, 教授 (70531391)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | マラリア / マクロファージ / LPSプレコンディショニング / trained innate immunity |
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| Outline of Final Research Achievements |
We investigated the protective effects of LPS preconditioning against lethal murine Plasmodium infection, focusing on liver macrophages, which are increased by LPS preconditioning. Mice were subjected to LPS preconditioning by intraperitoneal injections of low-dose LPS for 3 consecutive days, they were infected with pRBCs of P. yoelii 17XL. LPS preconditioning markedly increased the murine survival and reduced parasitemia. An in vitro phagocytic clearance assay of pRBCs showed that the CD11bhigh F4/80low liver macrophages in the LPS-preconditioned mice had significantly augmented phagocytic activity against pRBCs. The adoptive transfer of CD11bhigh F4/80low liver macrophages from LPS-preconditioned mice to control mice significantly improved survival after Plasmodium infection. We conclude that LPS preconditioning stimulated CD11bhigh F4/80low liver macrophages to augment the phagocytic clearance of pRBCs, which may play a central role in resistance against Plasmodium infection.
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| Free Research Field |
感染症学
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| Academic Significance and Societal Importance of the Research Achievements |
生体の炎症反応を抑制しつつ、マクロファージの殺菌能を増強させるLPSプレコンディショニングは、多剤耐性菌の感染予防に有効であることが明らかになりつつある。マラリア感染制御においては薬剤耐性原虫の出現、マラリアワクチン開発の遅れ等の問題を抱えている。そのため、感染の回避や軽減化を含めた、抗マラリア薬に頼らない、しかも効力の強い重症感染症対策の確立が求められている。貪食能の亢進をもたらすLPSプレコンディショニングによって薬剤耐性マラリア感染の感染防護が可能になれば、海外渡航者における感染症防護に資する所が極めて大きい。
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