Molecular mechanism of macrophage activation and intracellular parasitism by intracellular parasitic bacteria

细胞内寄生菌巨噬细胞活化及细胞内寄生的分子机制

• 批准号: 13226042
• 负责人: MITSUYAMA Masao
• 金额: $ 35.58万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13226042/
• 关键词: intracellular parasitic bacteria; Listeria monocvtogenes; Mycobacterium tuberculosis; macrophage; cytokine; listeriolysin O; リステリア; γインターフェロン; アポトーシス; ネクローシス; 細胞内寄生; カスパーゼ; 病原因子; エスケープ

(1) Listeriolysin 0 (LLO) is the major virulence factor of Listeria monocytogenas a representative intracellular parasitic bacteria, and exhibits a strong cytokine-inducing activity in addition to its role for the escape of this bacterium by cytolytic activity in the host macrophaes. Our study dearly showed that the cytokine-inducing activity, especially gammainterferon-inducing activity is dependent on the N-terminus while the cytolytic activity depends on the C-terminus(2) It was shown that all the cytokine-inducing CDC family proteins including LW filbt activate macrophages far IL-12 and IL-18 and. these macrophage-derived cytokines in turn stimulate NK cells for gamma interferon production that is essential for the induction of Thl-dependent protective immunity(3) There is a significant difference in the cytokine-inducing ability among LLO and allied proteins produced by Listeria seeligeri and Listeria ivanovii. We were able to show that such a difference is highly dependent on the structural difference at the N-terminus domain. A contribution of unique molecule recognizing LLO inside macrophage cytosol was also suggested.(4) Thl cytokine induction by Mycobacterium tuberculosis requires the stimulation with viable bacteria. It was shown that some growing bacteria-derive factor that depends on bacterial metabolism is required.(5) In experimental model of allergic condition in mice, LLO and allied protein with Thl cytokine-inducing activity were effective for the alleviation and control of allergic response.

(1)李斯特菌溶血素0（Listeriolysin 0，LLO）是单核细胞增生李斯特菌（Listeria monocytogenas）的主要毒力因子，除具有溶细胞逃逸作用外，还具有很强的诱生烟碱活性。我们的研究清楚地表明，精氨酸诱导活性，特别是γ-干扰素诱导活性依赖于N-末端，而细胞溶解活性依赖于C-末端。这些巨噬细胞衍生的细胞因子又刺激NK细胞产生γ干扰素，这对于诱导Th 1依赖性保护性免疫是必需的。（3）在由李斯特菌和李斯特菌产生的LLO和相关蛋白质之间，在精氨酸诱导能力上存在显著差异。我们能够表明，这种差异是高度依赖于在N-末端结构域的结构差异。巨噬细胞胞质溶胶内识别LLO的独特分子的贡献也被提出。(4)由结核分枝杆菌诱导的Thl细胞因子需要用活细菌刺激。结果表明，需要一些依赖于细菌代谢的生长细菌衍生因子。(5)在小鼠变态反应模型中，LLO和具有Th 1细胞因子诱导活性的同源蛋白对减轻和控制变态反应是有效的。

项目成果

Limited contribution of Toll-like receptor (TLR) 2 and TLR4 to the host response to a fungal infectious pathogen, Cryptococcus neoformans

Toll 样受体 (TLR) 2 和 TLR4 对宿主对真菌传染性病原体新型隐球菌的反应的贡献有限

• 发表时间: 2006
• 期刊: FEMS Immunology and Medical Microbiology 47(1)
• 作者: Kiwamu Nakamura;Kazuya Miyagi;Yoshinobu Koguchi;Yuki Kinjo;Kaori Uezu;Takeshi Kinjo;Morikazu Akamine;Jiro Fujita;Ikuo Kawamura;Masao Mitsuyama;Yoshiyuki Adachi;Naohito Ohno;Kiyoshi Takeda;Shizuo Akira;Akiko Miyazato;Mitsuo Kaku;and Kazuyos
• 通讯作者: and Kazuyos

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

不同细菌配体对小鼠鼻炎模型中过敏性炎症的改变：肥大细胞和树突状细胞的参与

• 发表时间: 2006
• 期刊: Clinical and Experimental Allergy 36(6)
• 作者: Kazuhiro Yamamoto;Ikuo Kawamura;Juichi Ito;and Masao Mitsuyama
• 通讯作者: and Masao Mitsuyama

Sporothrix schenkii thermo-tolerant mutants losing fatal visceral infectivity but retaining high cutaneous infectivity.

申基孢子丝耐热突变体失去了致命的内脏感染性，但保留了较高的皮肤感染性。

• 发表时间: 2001
• 期刊: Med. Mycol. 39
• 作者: Yajima T;Nishimura H;Ishimitsu R;Watase T;Busch DH;Pamer EG Kuwano H;Yoshikai Y.;Baba H 他7名;Ito Y 他8名;Tachibana T 他3名
• 通讯作者: Tachibana T 他3名

Role of macrophage scanvenger receptors in response to Listeria monocytogenes infection in mice.

巨噬细胞清道夫受体在小鼠单核细胞增生李斯特菌感染中的作用。

• 发表时间: 2001
• 期刊: Amer. J. Pathol. 158
• 作者: Yajima T;Nishimura H;Ishimitsu R;Watase T;Busch DH;Pamer EG Kuwano H;Yoshikai Y.;Baba H 他7名;Ito Y 他8名;Tachibana T 他3名;Ishiguro T 他7名
• 通讯作者: Ishiguro T 他7名

メルクマニュアル日本語版第18版(監訳)

默克手册日文版第18版（监修）

• 发表时间: 2006
• 作者: 山田久方;吉開泰信;光山正雄;光山正雄
• 通讯作者: 光山正雄