Delayed inflammatory response to primary pneumonic plague occurs in both outbred and inbred mice
Delayed inflammatory response to primary pneumonic plague occurs in both outbred and inbred mice
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DOI：
10.1128/iai.00403-06
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发表时间：
2007-02-01
影响因子：
3.1
通讯作者：
Dube, Peter H.
中科院分区：
文献类型：
--
作者：
Bubeck, Sarah S.;Cantwell, Angelene M.;Dube, Peter H.
鼠疫耶尔森氏菌是鼠疫的病原体，这种疾病可以表现为腺鼠疫或肺鼠疫。鼠疫的一个有趣的特征是它是一种快速发展的疾病，这表明鼠疫杆菌要么逃避和/或抑制对感染的先天免疫反应。因此，研究了两个品系的小鼠在原发肺鼠疫过程中的早期宿主反应，即近交系CD1和近交系C57BL/6。对这两个品系小鼠的病程的比较分析表明，这两个品系的小鼠对鼻腔感染鼠疫耶尔森氏菌CO92很敏感，并且在肺、肝和脾的定植方面具有相似的50%致死量和感染动力学。值得注意的是，在两个品系的小鼠中，直到感染后48小时才观察到强健的中性粒细胞募集到肺部，这表明炎症细胞募集到感染部位的时间有所延迟。此外，肺泡灌洗液中的促炎细胞因子(IL-6、肿瘤坏死因子α、干扰素、IL-12p70、单核细胞趋化蛋白1)和趋化因子(KC、MIP-2)直到感染后48h才能检测到，这与中性粒细胞(PMN)向肺内募集的增加相一致。相比之下，肺炎克雷伯菌引起的革兰氏阴性肺炎CD1小鼠在感染早期就表现出强烈的炎症反应，感染后24小时肺泡灌洗液中的PMN占大多数，表明这种感染比鼠疫杆菌感染更早地将PMN募集到肺中。总之，我们的结果表明，在原发鼠疫肺炎小鼠模型中，中性粒细胞向肺内募集的时间延迟，这与近交系和近交系小鼠的促炎细胞因子和趋化因子的延迟表达有关。
Yersinia pestis is the causative agent of plague, a disease that can manifest as either bubonic or pneumonic plague. An interesting feature of plague is that it is a rapidly progressive disease, suggesting that Y. pestis either evades and/or suppresses the innate immune response to infection. Therefore, the early host response during the course of primary pneumonic plague was investigated in two mouse strains, the outbred strain CD1 and the inbred strain C57BL/6. A comparative analysis of the course of disease in these two strains of mice indicated that they are susceptible to intranasal Y. pestis CO92 infection and have similar 50% lethal doses and kinetics of infection with respect to colonization of the lung, liver, and spleen. Significantly, in both strains of mice, robust neutrophil recruitment to the lungs was not observed until 48 h after infection, suggesting that there was a delay in inflammatory cell recruitment to the site of infection. In addition, proinflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha, gamma interferon, IL-12p70, monocyte chemoattractant protein 1) and chemokines (KC, MIP-2) in the bronchoalveolar lavage fluids were not readily detected until 48 h after infection, which coincided with the increase in polymorphonuclear leukocyte (PMN) recruitment to the lungs. In comparison, CD1 mice with gram-negative pneumonia caused by Klebsiella pneumoniae exhibited strong inflammatory responses early in infection, with PMNs comprising the majority of the cells in the bronchoalveolar lavage fluid 24 h postinfection, indicating that PMN recruitment to the lungs could occur earlier in this infection than in Y. pestis infection. Together, our results indicate that there is a delay in the recruitment of neutrophils to the lungs in the mouse model of primary plague pneumonia that correlates with delayed expression of proinflammatory cytokines and chemokines in both outbred and inbred mice.