| Project/Area Number |
18590400
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kyushu University |
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Principal Investigator |
HISAEDA Hajirme Kyushu University, Grad. Sch. of Med. Sci., Associate Professor (50243689)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,080,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | malaria / immune evasion / regulatory T cells / dendritic cells / Toll-like receptor 9 / トリプトファン代謝 / IDO |
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| Research Abstract |
Malaria is still one of the most life-threatening infectious diseases worldwide.Ingenious strategies for immune escape by malaria parasites prevent the development of sterile immunity, resulting in repeated symptomatic infections throughout the life of the host. Therefore, an understanding of this evasion mechanism is important for the effective control of malaria. We previously reported that immune escape of malaria parasites requires activation of immune suppressive regulatory T cells (Tregs). In this project, we have analyzed the mechanisms underlying activation of Tregs during murine malaria model.
Infection of mice with the rodent malaria parasite Plasmodium yoelii 17XL strain activates Tregs, leading to enhancement of their suppressive function. Using this enhancement in suppressive function as indicator of Treg activation, in vitro activation of Tregs requires the interaction of DCs with parasitized red blood cells (pRBCs)after phagocytosis. DCs stimulated with pRBCs could activa
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te OVA-specific Tregs, indicating that activation of Tregs occurs in an antigen-nonspecific manner. These results support the hypothesis that pRBCs deliver some signals to DCs to activate Tregs. We next examined the involvement of Toll-like receptor (TLR)signaling in this interaction between DCs and pRBCs, and found that TLR9 and MyD88 expressed by DCs are indispensable for activation of Tregs. Furthermore, TLR9-deficient mice showed the failure of Treg activation and subsequent development of protective T cells after infection with the malaria parasites and a partial resistance to the infection. There results clearly demonstrate that malaria parasites require TLF9 to activate Tregs for immune escape.
In conclusion, we propose a novel model for the functional regulation of Tregs as well as for the immune escape of malaria parasites, which may enable us to establish new approaches to developing effective immunity against malaria or preventing autoimmunity by correcting the balance between Tregs and effector/pathogenic T cells. Less
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