Elucidation of novel innate immune system by analysis of host-parasite interaction

通过分析宿主-寄生虫相互作用阐明新型先天免疫系统

• 批准号: 23689029
• 负责人: YAMAMOTO Masahiro
• 金额: $ 17.56万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23689029/
• 关键词: インターフェロンγ; 自然免疫; トキソプラズマ原虫; 細胞自律的免疫系; 自然免疫系; ROP18; ATF6β; 免疫系

Interferon-g (IFN-g) is essential for host defense against intracellular pathogens. Stimulation of innate immune cells by IFN-g up-regulates ~2000 effector genes such as immunity-related GTPases including p65 guanylate-binding protein (GBP) family genes. We show that a cluster of GBP genes is required for host cellular immunity against the intracellular parasite Toxoplasma gondii. We generated mice deficient for all six GBP genes located on chromosome 3 by targeted chromosome engineering. Mice lacking Gbpchr3 were highly susceptible to T. gondii infection, resulting in increased parasite burden in immune organs. Furthermore, Gbpchr3-deleted macrophages were defective in IFN-g-mediated suppression of T. gondii intracellular growth. In addition, some members of Gbpchr3 restored the protective response against T. gondii in Gbpchr3-deleted cells. Thus, Gbpchr3 redundantly play a pivotal role in anti-T. gondii host defense by controlling IFN-g-mediated cellular innate immunity.

干扰素-g (IFN-g) 对于宿主防御细胞内病原体至关重要。 IFN-g 刺激先天免疫细胞上调约 2000 个效应基因，例如免疫相关 GTP 酶，包括 p65 鸟苷酸结合蛋白 (GBP) 家族基因。我们发现，宿主针对细胞内寄生虫弓形虫的细胞免疫需要一组 GBP 基因。我们通过靶向染色体工程培育出位于 3 号染色体上的所有 6 个 GBP 基因均存在缺陷的小鼠。缺乏 Gbpchr3 的小鼠非常容易受到弓形虫感染，导致免疫器官中的寄生虫负担增加。此外，Gbpchr3缺失的巨噬细胞在IFN-g介导的弓形虫细胞内生长抑制方面存在缺陷。此外，Gbpchr3的一些成员在Gbpchr3缺失的细胞中恢复了针对弓形虫的保护性反应。因此，Gbchr3 在抗 T 细胞中发挥着重要作用。通过控制 IFN-g 介导的细胞先天免疫来防御弓形虫宿主。

项目成果

A protozoan parasite Toxoplasma gondii manipulates host cell functions by effector molecules

原生动物寄生虫弓形虫通过效应分子操纵宿主细胞功能

• 发表时间: 2013
• 作者: Keishi Adachi;Risa Nakamura;Yoshio Osada;Masachika Senba;Koji Tamada;Shinjiro Hamano;Yamamoto M
• 通讯作者: Yamamoto M

A mechanism of innate immune evasion by a protozoan parasite

原生动物寄生虫的先天免疫逃避机制

• 发表时间: 2011
• 作者: 安井正佐也;田口徹;水村和枝;木山博資;Sekine K;Masahir o Yamamoto
• 通讯作者: Masahir o Yamamoto

Selective and Strain-specific NFAT4 activation by a Toxoplasma gondii polymorphic Dense Granule Protein GRA6

弓形虫多态致密颗粒蛋白 GRA6 选择性和菌株特异性 NFAT4 激活

• 发表时间: 2013
• 作者: Abe H.;Mochizuki S.;Ohara K.;Ueno M.;Ohiai H.;Kitagawa Y.;Hino O.;Sato H. and Okada Y.;Yamamoto M
• 通讯作者: Yamamoto M

Role of GBPs in innate host defense against an intracellular pathogen Toxoplasma gondii

GBP 在宿主针对细胞内病原体弓形虫的先天防御中的作用

• 发表时间: 2012
• 作者: 山本雅裕;大嶋淳;馬知秀;神山長慶;竹田潔;村瀬詩織,加藤健祐,田口徹,水村和枝;杉浦友香;Yamamoto M
• 通讯作者: Yamamoto M

Targeted disruption of an ATF6β-dependent host type I immunity by a Toxoplasma virulence factor ROP18

弓形虫毒力因子 ROP18 有针对性地破坏 ATF6β 依赖性宿主 I 型免疫

• 发表时间: 2011
• 作者: Suzuki E;Chiba T;Zen Y;Miyagi S;Tada M;Kanai F;Imazeki F;Miyazaki M;Iwama A;Yokosuka O;川村晃久;田口徹．;内藤篤彦;山本雅裕
• 通讯作者: 山本雅裕