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Analysis for regulatory mechanism of macrophage functions by Mycobacterium tuberculosis

结核分枝杆菌对巨噬细胞功能的调控机制分析

基本信息

批准号：
17590389
负责人：
KAWAMURA Ikuo
金额：
$ 2.3万
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：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

In the series of study, we investigated how Mycobacterium tuberculosis modulates cell death of macrophages and the cytokine production. A virulent H37Rv triggers necrosis of infected macrophages. It is supposed that the bacterium ultimately escapes macrophages by induction of necrosis. At the initial phase of infection, however, H37Rv avoids excessive necrosis of infected host cells through induction of caspase-9 activation. It has been shown that RD1 locus in genome of M. tuberculosis is involved in the virulence of bacteria and the necrosis-inducing ability. We found that RD1 appears to encode some components possibly playing a role in the induction of host cell necrosis by inducing damage of the mitochondrial inner membrane and causing ATP depletion. In addition, we found that M tuberculosis phagocytosed in macrophages appears to keep active metabolism inside cells and some metabolites but not structural components of bacteria trigger the production of cytokines that are important for development of Th1 cells. Furthermore, we focused on the interaction between M tuberculosis and alveolar epithelial cells because the cells play a role in the first-line of defense by producing chemokines and cytokines in the lung. Results showed that the interaction of cells with Mycobacterial mammalian cell entry protein 1A (Mce1A) that play a critical role in invasion of bacteria into cells did not induce production of chemokines. However, it may promote chemokine induction by augmenting the interaction between bacteria and epithelial cells.

本系列研究探讨了结核分枝杆菌如何调节巨噬细胞的死亡和细胞因子的产生。致命的H37 Rv引发感染的巨噬细胞坏死。据推测，细菌最终通过诱导坏死而逃离巨噬细胞。然而，在感染的初始阶段，H37 Rv通过诱导半胱天冬酶-9活化来避免感染的宿主细胞的过度坏死。结果表明，M.结核病涉及细菌的毒力和坏死诱导能力。我们发现，RD 1似乎编码的一些组件可能在诱导宿主细胞坏死中发挥作用，通过诱导线粒体内膜的损伤和引起ATP耗竭。此外，我们还发现巨噬细胞吞噬的结核分枝杆菌似乎在细胞内保持活跃的代谢，并且一些代谢产物而不是细菌的结构成分触发了对Th 1细胞发育重要的细胞因子的产生。此外，我们专注于结核分枝杆菌和肺泡上皮细胞之间的相互作用，因为这些细胞通过在肺中产生趋化因子和细胞因子在第一线防御中发挥作用。结果表明，细胞与分枝杆菌哺乳动物细胞进入蛋白1A（Mce 1A）的相互作用，在细菌侵入细胞中发挥关键作用，不诱导产生趋化因子。然而，它可能通过增强细菌和上皮细胞之间的相互作用来促进趋化因子的诱导。

项目成果

期刊论文数量（38）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mycobacterial mammalian cell entry protein 1A (Mce 1A)-mediated adherence enhances the chemokine production by A549 alveolar epithelial cells

分枝杆菌哺乳动物细胞进入蛋白 1A (Mce 1A) 介导的粘附增强 A549 肺泡上皮细胞趋化因子的产生

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Mitsuyama;M.;and Kawamura;I
通讯作者：
I

Listeriolysin O derived from Listeria monocytogenes inhibits the effector phase of an experimental allergic rhinitis induced by ovalbumin in mice

DOI：
10.1111/j.1365-2249.2006.03092.x
发表时间：
2006-06-01
期刊：
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
影响因子：
4.6
作者：
Yamamoto, K.;Kawamura, I.;Mitsuyama, M.
通讯作者：
Mitsuyama, M.

Involvement of caspase-9 in the induction of necrosis of RAW 264 cells infected with Mycobacterium tuberculosis

Caspase-9参与诱导结核分枝杆菌感染的RAW 264细胞坏死

DOI：
发表时间：
2007
期刊：
Infection and Immunity 75
影响因子：
0
作者：
川本;進;Ryosuke Uchiyama
通讯作者：
Ryosuke Uchiyama

Modification of allergic inflammation in murine model of rhinitis by different bacterial ligands : involvement of mast cells and dendritic cells

不同细菌配体对小鼠鼻炎模型过敏性炎症的改变：肥大细胞和树突状细胞的参与

DOI：
发表时间：
2006
期刊：
Clinical Experimental Allergy
影响因子：
0
作者：
Tomoyasu;T et al.;Isao Watanabe;Osaki Takako;Aosai F.;Kazuhiro Yamamoto;Hiroyuki Yamaguchi;Matsushima R. et al.;Takano Riho;Takahashi A. et al.;Norose K.;Kazuhiro Yamamoto
通讯作者：
Kazuhiro Yamamoto

Modification of allergic inflammation in murine model of rhinitis by different bacterial ligands : involvement of mast

不同细菌配体对小鼠鼻炎模型中过敏性炎症的改变：肥大的参与