Pulmonary and systemic host response to Streptococcus pneumoniae and Klebsiella pneumoniae in normal and immunosuppressed mice
Pulmonary and systemic host response to Streptococcus pneumoniae and Klebsiella pneumoniae in normal and immunosuppressed mice
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DOI：
10.1128/iai.69.9.5294-5304.2001
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发表时间：
2001-09-01
影响因子：
3.1
通讯作者：
Bergeron, MG
中科院分区：
文献类型：
--
作者：
Wang, EJ;Ouellet, N;Bergeron, MG
与菌源性肺炎相关的死亡率仍然很高，败血症在炎症、肺损伤和死亡中的作用仍不清楚，主要是在白细胞减少状态下。在本研究中，在免疫功能正常和白细胞减少小鼠的菌血症实验模型中，测定了微生物学、组织病理学和宿主对肺炎链球菌和肺炎克雷伯菌感染的反应。环磷酰胺对白细胞的消耗不影响肺炎球菌从血液中的早期清除，但促进了肺部的生长。相比之下，克雷伯菌在白细胞减少小鼠的血液中迅速生长。这些观察结果表明，基于组织的吞噬细胞和循环白细胞分别在肺炎链球菌和肺炎克雷伯菌的根除中发挥重要作用。肺炎链球菌菌血症期间肺中白细胞募集的动力学表明，免疫功能正常小鼠的早期强烈炎症与肿瘤坏死因子α释放和组织学紊乱有关，包括肺泡间隙的细胞碎片和表面活性剂。白细胞耗竭进一步刺激肺炎链球菌和肺炎克雷伯菌血症的肺毛细血管渗漏，这似乎可归因于细菌毒力因素。一氧化氮的产生在各组间无显著差异。白细胞减少和血小板计数低是两种菌株菌血症晚期的特征，但只有肺炎克雷伯菌改变了肾功能。了解菌血症的发病机制将有助于建立对败血症和肺炎有益的治疗方法。
Mortality related to bacteremic pneumonia remains high, and the role of sepsis in inflammation, pulmonary injury, and death remains unclear, mostly in leukopenic states. In the present study, the microbiology, histopathology, and host response to Streptococcus pneumoniae and Klebsiella pneumoniae infection were determined in an experimental model of bacteremia in immunocompetent and leukopenic mice. Leukocyte depletion by cyclophosphamide did not impair the early clearance of pneumococci from blood but facilitated growth in lungs. By contrast, klebsiellae rapidly grew in blood of leukopenic mice. These observations suggest that tissue-based phagocytes and circulating leukocytes, respectively, play prominent roles in S. pneumoniae and K. pneumoniae eradication. The kinetics of leukocyte recruitment in lungs during S. pneumoniae bacteremia suggested early strong inflammation in immunocompetent mice that is associated with tumor necrosis factor alpha release and histological disorders, including cell debris and surfactant in alveolar spaces. Leukocyte depletion further stimulated pulmonary capillary leakage both in S. pneumoniae and K. pneumoniae bacteremia, which seemed attributable to bacterial virulence factors. Nitric oxide production did not differ significantly among groups. Leukopenia and low platelet counts characterized the late stage of bacteremia for both strains, but only K. pneumoniae altered renal function. Understanding the pathogenesis of bacteremia will help establish beneficial therapies for both sepsis and pneumonia.