Analyses for immune evasion by malaria parasites

疟原虫免疫逃避分析

• 批准号: 18590400
• 负责人: HISAEDA Hajirme
• 金额: $ 2.61万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590400/
• 关键词: malaria; immune evasion; regulatory T cells; dendritic cells; Toll-like receptor 9; トリプトファン代謝; IDO

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 … More 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

疟疾仍然是全世界最威胁生命的传染病之一。疟疾寄生虫采取免疫环境的策略阻止了无菌免疫学的发展，从而在宿主的整个生命中都反复出现症状感染。因此，对这种进化机制的理解对于对疟疾的有效控制很重要。我们先前报道说，疟疾寄生虫的免疫逃逸需要激活免疫抑制性调节性T细胞（Tregs）。在该项目中，我们分析了鼠类疟疾模型期间Treg激活的基础机制。与啮齿动物疟原虫寄生虫质子疟原虫17xl菌株的小鼠感染可激活Tregs，从而增强其抑制功能。在抑制功能中使用这种增强作为Treg激活的指标，Tregs的体外激活需要DC在吞噬作用后与寄生的红细胞（PRBC）相互作用。用PRBC刺激的DC可以进行活动……更多的特异性Treg，表明Treg的激活是以抗原非特异性方式发生的。这些结果支持以下假设：PRBC向DC传递一些信号以激活Treg。接下来，我们检查了DCS和PRBC之间这种相互作用的Toll样受体（TLR）信号的参与，发现DC表达的TLR9和MYD88对于激活Treg是必不可少的。此外，TLR9缺陷小鼠在感染疟原虫寄生虫感染后的Treg激活和随后的受保护T细胞的破坏以及对感染的部分耐药性。结果清楚地表明，疟疾寄生虫需要TLF9激活TREG以进行免疫逃生。总之，我们为TREG的功能调节以及疟疾寄生虫的免疫逃生提供了一种新型模型，这可能使我们能够建立针对Malaria的有效免疫或预防自动免疫的新方法，或者通过纠正Tregs/Tregs/Tregs/Tregs/perneg and/tregmunity。较少的

项目成果

Toda's New Bacteriology

户田新细菌学

• 发表时间: 2007
• 作者: S.;Yoshida;Y.;Yanagi;Y.;Yoshikai
• 通讯作者: Yoshikai

Malaria parasite induces tryptophan-related immune suppression in mice

• DOI: 10.1017/s0031182007002326
• 发表时间: 2007-07-01
• 期刊: PARASITOLOGY
• 影响因子: 2.4
• 作者: Tetsutani, K.;To, H.;Himeno, K.
• 通讯作者: Himeno, K.

Malaria parasites require TLR9 signaling for immune evasion by activating regulatory T cells

• DOI: 10.4049/jimmunol.180.4.2496
• 发表时间: 2008-02-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Hisaeda, Hajime;Tetsutani, Kohhei;Himeno, Kunisuke
• 通讯作者: Himeno, Kunisuke

Pathological role of Toll-like receptor sigaling in cerebral malaria.

Toll 样受体信号传导在脑型疟疾中的病理作用。

• 发表时间: 2007
• 期刊: International Immunology 19
• 作者: Tetsutani;K.;et. al.;Tetsutani K et al.;Tao K et al.;Coban C et al.
• 通讯作者: Coban C et al.

TLR-dependent induction of IFN- mediates host defense against Trypanosoma cruzi

TLR 依赖性 IFN-介导宿主对克氏锥虫的防御

• 发表时间: 2006
• 期刊: Journal of Immunology 177
• 作者: Tetsutani;K.;et. al.;Tetsutani K et al.;Tao K et al.;Coban C et al.;Koga R et al.
• 通讯作者: Koga R et al.