Tam M, Snipes G J, Stevenson M M
Centre for the Study of Host Resistance, Montreal General Hospital Research Institute; and Department of Neuropathology, Montreal, Canada.
Am J Respir Cell Mol Biol. 1999 Apr;20(4):710-9. doi: 10.1165/ajrcmb.20.4.3223.
Chronic bronchopulmonary Pseudomonas aeruginosa infection, initiated by intratracheal instillation of 1 to 2 x 10(5) colony-forming units of a mucoid strain of bacteria trapped in agar beads, was characterized in resistant BALB/c mice and susceptible C57BL/6 (B6) mice through 28 d postinfection. B6 mice experienced a more severe infection than BALB/c mice as evidenced by significantly higher mortality and significantly greater weight loss during the first 14 d. Furthermore, B6 mice had significantly higher numbers of bacteria in the lungs through 21 d after infection. Overall, only 22% of these hosts cleared the infection. In contrast, 67% of BALB/c mice cleared the infection. These differences between resistant and susceptible mice were found to correlate with histopathologic differences in the type of inflammation and the extent of tissue damage. An acute, predominantly neutrophilic inflammation and extensive tissue damage were apparent in the lungs of susceptible B6 mice, whereas chronic, granulomatous inflammation and little or no tissue damage were visible in resistant BALB/c mice. The finding of acute inflammation in the lungs of infected B6 mice was confirmed by fluorescence-activated cell sorter (FACS) analyses, which demonstrated that these mice had significantly greater proportions of polymorphonuclear neutrophils in the lungs on Days 7 and 14 after infection than did BALB/c mice. FACS analyses also revealed significant and similar increases in CD3(+) lung cells in both strains as the infection progressed. The CD4/CD8 ratio was significantly greater in BALB/c mice by 21 d after infection when the majority of these animals, but not B6 mice, had cleared the infection.
通过气管内注入被困在琼脂珠中的1至2×10⁵个黏液样菌株的菌落形成单位引发慢性支气管肺铜绿假单胞菌感染,在感染后28天对耐药的BALB/c小鼠和易感的C57BL/6(B6)小鼠进行了特征分析。B6小鼠比BALB/c小鼠经历了更严重的感染,这在感染后的前14天表现为显著更高的死亡率和显著更大的体重减轻。此外,感染后21天内,B6小鼠肺部的细菌数量显著更高。总体而言,这些宿主中只有22%清除了感染。相比之下,67%的BALB/c小鼠清除了感染。发现耐药和易感小鼠之间的这些差异与炎症类型和组织损伤程度的组织病理学差异相关。在易感的B6小鼠肺部明显可见急性、主要为中性粒细胞性炎症和广泛的组织损伤,而在耐药的BALB/c小鼠肺部可见慢性、肉芽肿性炎症且几乎没有或没有组织损伤。通过荧光激活细胞分选仪(FACS)分析证实了感染的B6小鼠肺部存在急性炎症,该分析表明这些小鼠在感染后第7天和第14天肺部多形核中性粒细胞的比例比BALB/c小鼠显著更高。FACS分析还显示,随着感染的进展,两种品系的CD3⁺肺细胞均有显著且相似的增加。感染后21天,当大多数BALB/c小鼠(而非B6小鼠)清除感染时,BALB/c小鼠的CD4/CD8比值显著更高。