Molecular mechanisms of bone-specific immunopathology during malaria
| Project/Area Number |
16H05181
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Parasitology (including sanitary zoology)
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| Research Institution | Osaka University |
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Principal Investigator |
Cevayir Coban 大阪大学, 免疫学フロンティア研究センター, 教授 (00397712)
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| Research Collaborator |
ISHII Ken
AKIRA Shizuo
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | Bone loss / osteoclast / osteoblast / malaria / Vitamin D / RANKL / MyD88 / Plasmodium / Malaria / bone loss / plasmodium products / tissue specificity / osteoporosis / hemozoin / Hemozoin / Bone / chronic infection / Bone homeostasis / Chronic infection / Immunology |
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| Outline of Final Research Achievements |
Malaria has deadly complications; however, the long term pathological consequences of chronic malaria infection are poorly understood. We suspected that there is an association between growth retardation and malaria infection. Therefore, we investigated possible negative impact of malaria infection on bone remodeling and growth. Using mouse models mimicking chronic and self-clearing Plasmodium infection we showed that infection causes significant and long term bone loss in adult mice and growth retardation in young mice. Bone remodeling is completely suppressed during the acute phase of infection, but is highly activated immediately after the clearance of parasites, with increased osteoclastic activity skewing the balance toward bone resorption. Osteoclasts are activated by the key osteclastogenic cytokine RANKL, which was upregulated in osteoblasts through MyD88-dependent inflammation, triggered by the accumulation and long term persistence of parasite products in the bone marrow.
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| Academic Significance and Societal Importance of the Research Achievements |
Our results highlight the risk of bone loss in malaria-infected patients. Bone loss is sustained even after recovery from malaria.Therapies promoting bone health like Vitamin D treatment coupled with anti-malarial treatment may help to improve bone health in malaria-infected individuals.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] A distinct subpopulation of CD25－ T-follicular regulatory cells localizes in the germinal centers2017
Author(s)
James Badger Wing, Yohko Kitagawa, Michela Locci, Hannah Hume, Christopher Tay, Takayoshi Morita, Yujiro Kidani, Kyoko Matsuda, Takeshi Inoue, Tomohiro Kurosaki, Shane Crotty, Cevayir Coban, Naganari Ohkura, and Shimon Sakaguchi
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Journal Title
Proceedings of the National Academy of Sciences
Volume: 114
Issue: 31
Pages: 6400-6400
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Plasmodium products persist in the bone marrow and promote chronic bone loss2017
Author(s)
Lee MSJ, Maruyama K, Fujita Y, Konishi A, Lelliott PM, Itagaki S, Horii T, Lin JW, Khan SM, Kuroda E, Akira S, Ishii KJ, Coban C.
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Journal Title
Science Immunology
Volume: 2
Issue: 12
Pages: 2-2
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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