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.

在这一系列研究中，我们研究了结核分枝杆菌如何调节巨噬细胞的细胞死亡和细胞因子的产生。剧毒的 H37Rv 会引发受感染巨噬细胞坏死。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，H37Rv 通过诱导 caspase-9 激活来避免受感染宿主细胞的过度坏死。研究表明，结核分枝杆菌基因组中的RD1位点与细菌的毒力和坏死诱导能力有关。我们发现 RD1 似乎编码一些可能通过诱导线粒体内膜损伤并导致 ATP 耗竭而诱导宿主细胞坏死的成分。此外，我们发现被巨噬细胞吞噬的结核分枝杆菌似乎可以保持细胞内活跃的新陈代谢，并且一些代谢物（而不是细菌的结构成分）触发细胞因子的产生，这对 Th1 细胞的发育很重要。此外，我们还关注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而在第一道防线中发挥作用。结果表明，细胞与分枝杆菌哺乳动物细胞进入蛋白 1A (Mce1A) 的相互作用在细菌侵入细胞中起关键作用，但不会诱导趋化因子的产生。然而，它可以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）

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.

Listeriolysin 0 derived from Listeria monocytogenes inhibits the effector phase of an experimental allergic rhinitis

源自单核细胞增生李斯特菌的李斯特菌溶血素 0 可抑制实验性过敏性鼻炎的效应期

DOI：
发表时间：
2006
期刊：
Clinical and Experimental Immunology 144 (3)
影响因子：
0
作者：
Kazuhiro Yamamoto;Ikuo Kawamura;Takanari Tominaga;Takamasa Nomura
通讯作者：
Takamasa Nomura

Streptomycin-dependent exhibition of cytokine-inducing activity in streptomycin-dependent Mycobacterium tuberculosis strain 18b

链霉素依赖性结核分枝杆菌菌株 18b 中链霉素依赖性细胞因子诱导活性的表现

DOI：
发表时间：
2005
期刊：
Infection and Immunity 73
影响因子：
0
作者：
Hagi;A.;Yutaka Fukazawa
通讯作者：
Yutaka Fukazawa

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