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

我们在肺炎动物模型和体外巨噬细胞实验中研究了军团菌感染的发病机制和抗军团菌感染的新策略。1.分析小鼠肺炎模型的宿主反应。在军团菌肺炎的小鼠模型中，我们观察到TLR-2是识别军团菌内毒素的关键分子。此外，我们的数据显示，在高氧环境下，Fas缺陷小鼠对军团菌感染具有更强的抵抗力，这表明Fas分子在军团菌肺炎的发病机制中发挥了作用。2.高氧对军团菌肺炎的影响在肺炎小鼠模型中，我们观察了亚致死性高氧(90%氧气作用60h)对军团菌肺炎的影响。这些数据清楚地表明，高氧夸大了军团菌肺炎的致死性，这与肺细胞加速凋亡有关。我们还检测了几种化合物，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。3.在军团菌肺炎大鼠模型中，我们仔细研究了高浓度氧气和高氧持续时间对大鼠肺炎的影响。4.肺炎军团菌中碎片蛋白的作用我们研究了碎片蛋白在军团菌肺炎发病机制中的作用，发现碎片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是细胞胞液空间中微生物分子的模式识别受体。

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.