Regulatory mechanism of the generation of immune response to Mycobacterium tuberculosis infection

结核分枝杆菌感染免疫应答产生的调控机制

• 批准号: 21590479
• 负责人: KAWAMURA Ikuo
• 金额: $ 3万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590479/
• 关键词: 結核菌; PD-1; PPE37; マクロファージ; T細胞; IL-1α; IFN-γ; サイトカイン; BCG; M. bovis BCG; マクロフアージ; 感染防御免疫; PD-L1

This study was carried out to find out the molecular mechanism as to how Mycobacterium tuberculosis and M. bovis BCG regulate the immune response in infected host. The research revealed that the RD1 locus in the M. tuberculosis genome, which is highly implicated in bacterial virulence, is involved in the production of IL-1α, IL-1βand IL-18 by promoting the activation of calpain and caspase-1, respectively. In addition, it is probable that mycobacterial PPE37 protein contributes to the inhibition of IL-6 and TNF-αproduction from infected macrophages. Moreover, it has been shown that the PD-1 signal pathway is required for the suppression of hyper-immune response to M. tuberculosis infection. On the other hand, it is certain that the efficacy of BCG vaccination is enhanced by the impediment of signal pathway.

本研究旨在探讨结核分枝杆菌与M。BCG调节感染宿主的免疫应答。研究结果表明，M.与细菌毒力高度相关的结核杆菌基因组分别通过促进钙蛋白酶和半胱天冬酶-1的活化而参与IL-1α、IL-1β和IL-18的产生。此外，分枝杆菌PPE 37蛋白可能有助于抑制感染巨噬细胞产生IL-6和TNF-α。此外，已经显示PD-1信号通路是抑制对M的超免疫应答所必需的。肺结核感染。另一方面，可以肯定的是，卡介苗接种的效果是通过信号通路的障碍而增强的。

项目成果

The role of inflammasomes in bacterial infections

炎症小体在细菌感染中的作用

• 发表时间: 2012
• 作者: 土屋晃介（筆頭縁者）;他
• 通讯作者: 他

Listeriolysin O-dependent bacterial entry into the cytoplasm is required for calpain activation and interleukin-1a secretion in macrophages infected with Listeria monocytogenes

李斯特菌溶血素 O 依赖性细菌进入细胞质是单核细胞增生李斯特菌感染的巨噬细胞中钙蛋白酶激活和白细胞介素 1a 分泌所必需的

• 发表时间: 2010
• 期刊: Infection and Immunity VOL.78
• 作者: Nariya H;Miyata S;Tamai E;Sekiya H;Maki J and Okabe A;Sita R.Dewamitta
• 通讯作者: Sita R.Dewamitta

The RD1 Locus in the Mycobacterium tuberculosis Genome Contributes to Activation of Caspase-1 via Induction of Potassium Ion Efflux in Infected Macrophages

• DOI: 10.1128/iai.00015-09
• 发表时间: 2009-09-01
• 期刊: INFECTION AND IMMUNITY
• 影响因子: 3.1
• 作者: Kurenuma, Takeshi;Kawamura, Ikuo;Mitsuyama, Masao
• 通讯作者: Mitsuyama, Masao

Expression of the Mycobacterium tuberculosis PPE37 protein in Mycoba cterium smegmatis induces low TNF-α and IL-6 production in murine macrophages

耻垢分枝杆菌中结核分枝杆菌 PPE37 蛋白的表达诱导小鼠巨噬细胞中 TNF-α 和 IL-6 的低产量

• 发表时间: 2011
• 期刊: Journal of Medical Microbiology
• 影响因子: 3
• 作者: 清水健;野田公俊;長廻ゆりあ,重茂克彦,稲垣華絵,山本裕紀,胡東良,中根明夫,品川邦汎;小栗聡;Sylvia Daim
• 通讯作者: Sylvia Daim

Important role of ASC in resistance to Mycobacterium tuberculosis infection in vivo

ASC在体内抵抗结核分枝杆菌感染中的重要作用

• 发表时间: 2010
• 作者: S. R. Dewamitta;酒井俊佑;土屋晃介;原英樹;野村卓正;河村伊久雄;光山正雄
• 通讯作者: 光山正雄