2015 Fiscal Year Annual Research Report
マラリア感染における脳内免疫反応の4次元イメージング
| Project/Area Number |
25293100
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| Research Institution | Osaka University |
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Principal Investigator |
Coban Cevayir 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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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | Immunology / Cerebral Malaria / Imaging / MRI / Multiphoton imaging / Olfactory bulb / smell loss |
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| Outline of Annual Research Achievements |
Plasmodium falciparum infection in human manifest with a deadly complication called cerebral malaria (CM). It is characterized by sudden coma, death or long-term neurodisability if survived. Similar to various central nervous system inflammatory disorders, dysfunction of the blood-brain-barrier (BBB) is the main feature of CM; however, little is known how it occurs. Studies using a mouse model of experimental cerebral malaria (ECM) have indicated that BBB disruption and CD8 T cell recruitment contribute to disease, but the spatiotemporal mechanisms are poorly understood. We have approached to this problem by using cutting-edge imaging technologies. We have shown by ultra-high-field MRI and multiphoton microscopy that the olfactory bulb is physically and functionally damaged (loss of smell) by Plasmodium parasites during ECM. The trabecular small capillaries comprising the olfactory bulb show parasite accumulation and cell occlusion followed by microbleeding, events associated with high fever and cytokine storm. Specifically, the olfactory upregulates chemokine CCL21, and loss or functional blockade of its receptors CCR7 and CXCR3 results in decreased CD8 T cell activation and recruitment, respectively, as well as prolonged survival. Thus, early detection of olfaction loss and blockade of pathological cell recruitment may offer potential therapeutic strategies for CM.
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| Research Progress Status |
27年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
27年度が最終年度であるため、記入しない。
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| Causes of Carryover |
27年度が最終年度であるため、記入しない。
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| Expenditure Plan for Carryover Budget |
27年度が最終年度であるため、記入しない。
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