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

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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.