Induction and regulation of Protective immune responses against malaria parasites

针对疟疾寄生虫的保护性免疫反应的诱导和调节

• 批准号: 16590340
• 负责人: YUI Katsuyuki
• 金额: $ 2.3万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590340/
• 关键词: malaria; T cells; memory cells; dendritic cells; cytokine; macrophage; pattern recognition receptor; immune regulation; スポロゾイト; 防御免疫

1.Modulation of T-cell immune responses by malaria parasitesWe studied immune responses and the protective effect of CD4^+ T-cells in mice recovered from P.yoelii 17XNL infection. CD4^+ T-cells from spleen of mice recovered from malaria infection showed spesific proliferative responses. However, they produced limited levels of IL-2 and high levels of IL-10. Adoptive transfer of these purified CD4^+ T-cells could not confer protective immunity against sporozoite infection. These results suggested that CD4^+ T-cells in Plasmodium-infected mice are functionally modulated.2.Function of dendritic cells in malaria-infected miceWe characterized function of dendritic cells from mice infected with P.yoelii. Production of IL-12 in response to Toll-like receptor stimulation was reduced when compared with normal dendritic cells while IL-10 production was augmented. The ability to activate antigen specific T-cells was not reduced in both MHC class I and class II pathways. We will continue to study molecular mechanisms underlying augmented IL-10 production and function of T-cells activated by these dendritic cells.3.Function of IRF-4, transcription factor that regulates immune responses, in dendritic cells and macrophagesTranscription factor IRF-4 is expressed in immune cells including lymphocytes, dendritic cells and macrophages. We have revealed that IRF-4 plays a critical role for the differentiation of a subset of dendritic cells and has inhibitory role for the TLR-mediated signaling. This inhibition mainly regulates activation of MAP kinase JNK and NF-κB.

1.疟原虫对T细胞免疫反应的调节我们研究了从P.yoelii 17XNL感染中恢复的小鼠的免疫反应和CD4^+ T细胞的保护作用。从疟疾感染中恢复的小鼠脾脏中的 CD4^+ T 细胞显示出特异性的增殖反应。然而，它们产生的 IL-2 水平有限，而 IL-10 水平较高。这些纯化的 CD4^+ T 细胞的过继转移不能赋予针对子孢子感染的保护性免疫。这些结果表明疟原虫感染小鼠的CD4+T细胞受到功能调节。2.疟疾感染小鼠树突状细胞的功能我们对约氏疟原虫感染小鼠的树突状细胞的功能进行了表征。与正常树突细胞相比，Toll 样受体刺激后 IL-12 的产生减少，而 IL-10 的产生增加。 MHC I 类和 II 类途径中激活抗原特异性 T 细胞的能力均未降低。我们将继续研究树突状细胞激活的T细胞增加IL-10产生和功能的分子机制。3.树突状细胞和巨噬细胞中调节免疫反应的转录因子IRF-4的功能转录因子IRF-4在包括淋巴细胞、树突状细胞和巨噬细胞在内的免疫细胞中表达。我们发现 IRF-4 对树突状细胞亚群的分化起着关键作用，并对 TLR 介导的信号传导具有抑制作用。这种抑制主要调节 MAP 激酶 JNK 和 NF-κB 的激活。

项目成果

Negative regulation of Toll-like-receptor signaling by IRF-4

• DOI: 10.1073/pnas.0508327102
• 发表时间: 2005-11-01
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Negishi, H;Ohba, Y;Honda, K
• 通讯作者: Honda, K

Critical roles of interferon regulatory factor-4 in CD11b^<high>CD8a^- dendritic cell development

干扰素调节因子 4 在 CD11b^<high>CD8a^- 树突状细胞发育中的关键作用

• 发表时间: 2004
• 期刊: Proc.Natl.Acad.Sci.USA. 101
• 作者: S.Fukumoto;K.Miura;S.Suzuki et al.
• 通讯作者: S.Suzuki et al.

Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS

• DOI: 10.1073/pnas.0504226102
• 发表时间: 2005-11-01
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Honma, K;Udono, H;Yui, K
• 通讯作者: Yui, K

Critical roles of interferon regulatory factor 4 in CD11bhighCD8α- dendritic cell development

• DOI: 10.1073/pnas.0402139101
• 发表时间: 2004-06-15
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Suzuki, S;Honma, K;Kumatori, A
• 通讯作者: Kumatori, A

Hsp-antigen fusion and their use for immunization

Hsp-抗原融合及其在免疫中的用途

• 发表时间: 2004
• 期刊: Methods 32
• 作者: Ishii;G.;Ochiai;A.;et al.;H.Udono et al.
• 通讯作者: H.Udono et al.