Research for analysis of pathogenesis and development of a novel strategy for Legionella infection

军团菌感染发病机制分析及新策略开发研究

• 批准号: 16390289
• 负责人: TAKEDA Kazuhiro
• 金额: $ 8.96万
• 依托单位: Toho University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390289/
• 关键词: Legionella; Pneumonia; Pathogenesis; Apoptosis; Cytokines

We have examined pathogenesis of and a novel strategy agains Legionella infection in animal model of pneumonia and in-vitro macrophage experiments.1.Analysis of host responses in mouse pneumonia modelIn mouse model of Legionella pneumonia using several kinds of knock-out mice, such as Toll-like receptors (TLR) and Fas-deficient mice, we observed that TLR-2 is a critical for recognition of lipopolysaccharide of Legionella organism. In addition, our data showed that Fas-deficient mice are more resistant to Legionella infection in the setting of hyperoxia, which suggest a role of Fas molecule in pathogenesis of Legionella pneumonia.2.Effects of hyperoxia on Legion ella pneumoniaIn mouse model of pneumonia, we examined effects of sub-lethal hyperoxia (90% oxygen for 60 hours) on Legionella pneumonia. The data clearly demonstrated that hyperoxia exaggerates Legionella pneumonia in lethality, which was associated with accelerated apoptosis in pulmonary cells. Also we examined potential of several compounds, such as hepatocyte-growth factor and small interfering RNS, in mouse model of pneumonia and in-vitro infection experiments. Our data demonstrated beneficial effects of siRNA for caspase-3 on Legionella infection model.3.In rat model of Legionella pneumoniaIn rat model of pneumonia, we carefully examined effects of higher concentrations of oxygen and duration of hyperoxia. The data demonstrated exaggeration of acute lung injury in an oxygen-concentration and duration-time dependent fashion.4.Role of fragellin protein in Legionella pneumoniaWe examined role of fragellin in pathogenesis of Legionella pneumonia, and found that fragellin protein is a critical molecule for recognition of Legionella by macrophages. Also our data suggest NOD as a pattern recognition receptor for microbial molecules in cytosolic space of the cells.

本研究通过动物肺炎模型和体外巨噬细胞实验，探讨了军团菌感染的发病机制和新的抗军团菌感染策略。1.小鼠肺炎模型中宿主反应的分析在利用Toll样受体（TLR）基因敲除小鼠和Fas基因敲除小鼠建立的军团菌肺炎模型中，我们观察到TLR-2是军团菌生物体识别脂多糖的关键。此外，我们的数据显示Fas基因缺陷小鼠在高氧环境下对军团菌感染的抵抗力更强，这提示Fas分子在军团菌肺炎的发病机制中起作用。2.高氧对军团菌肺炎的影响在小鼠肺炎模型中，我们研究了亚致死高氧（90%氧气60小时）对军团菌肺炎的影响。这些数据清楚地表明，高氧加重了军团菌肺炎的致死性，这与肺细胞的加速凋亡有关。此外，我们还研究了几种化合物，如肝细胞生长因子和小干扰RNS，在小鼠肺炎模型和体外感染实验中的潜力。我们的数据显示了caspase-3的siRNA对军团菌感染模型的有益作用。3.在军团菌肺炎大鼠模型中，我们仔细检查了高浓度氧和高氧持续时间的影响。4. fragellin蛋白在军团菌肺炎中的作用我们研究了fragellin蛋白在军团菌肺炎发病机制中的作用，发现fragellin蛋白是巨噬细胞识别军团菌的关键分子。此外，我们的数据表明NOD作为模式识别受体的微生物分子在细胞的胞质空间。

项目成果

Regulatory effects of macrolides on bacterial virulence: potential role as quorum-sensing inhibitors.

• DOI: 10.2174/1381612043383377
• 发表时间: 2004-09
• 期刊: Current pharmaceutical design
• 影响因子: 3.1
• 作者: K. Tateda;T. Standiford;J. Pechère;K. Yamaguchi

Azithromycin blocks neutrophil recruitment in Pseudomonas endobronchial infection

• DOI: 10.1164/rccm.200402-200oc
• 发表时间: 2004-12-15
• 期刊: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
• 影响因子: 24.7
• 作者: Tsai, WC;Rodriguez, ML;Standiford, TJ
• 通讯作者: Standiford, TJ

Legionella pneumophila evades gamma interferon-mediated growth suppression through interleukin-10 induction in bone marrow-derived macrophages.

嗜肺军团菌通过骨髓源性巨噬细胞中白细胞介素 10 的诱导来逃避 γ 干扰素介导的生长抑制。

• 发表时间: 2005
• 期刊: Infect Immun 73
• 作者: Horikawa M. et al.;Tateda K. et al.;Tanabe M. et al.;Horino T. et al.;Isozumi R. et al.;Yoshizawa S. et al.
• 通讯作者: Yoshizawa S. et al.