| Project/Area Number |
20K16234
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49040:Parasitology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
LEE MICHELLE 東京大学, 医科学研究所, 特任助教 (10821423)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Malaria / Bone marrow / Hematopoiesis / HSC niche / malaria / bone marrow niche / immunity / chronic inflammation / hematopoietic stem cells |
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| Outline of Research at the Start |
We previously found that chronic retention of the malaria parasite products in the bone marrow after recovery from malaria causes bone loss. This prompts the question whether malaria infection and the accumulation of parasite products in the bone marrow impose any impact to the bone marrow. This proposal aims to address the alteration of bone marrow niches and hematopoiesis during and after recovery from malaria infection, as well as to examine whether these changes contribute to compromised host immunity.
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| Outline of Final Research Achievements |
Hematopoiesis in the bone marrow is modulated by signals from mesenchymal cells that form the hematopoietic stem cell (HSC) niches. In this study, we found that malaria causes vasodilation, inhibits osteoblasts, and reduces a population of HSC niche supporting cells in the bone marrow. Gene transcriptomic analysis revealed that cytokines from these HSC niche supporting cells altered during malaria infection which led to impaired hematopoiesis and lymphopoiesis. We found that chronic asymptomatic malaria infection had a profound damage on bone marrow hematopoietic niches, raises the concern of asymptomatic cases that remain undiagnosed.
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| Academic Significance and Societal Importance of the Research Achievements |
This study reveals that infection such as malaria can modulate host immune responses by affecting bone marrow hematopoiesis through the alteration of bone marrow niches. This study suggests that malaria may have chronic impact on host immunity.
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