Cigarette Smoke Exposure Impairs Pulmonary Bacterial Clearance and Alveolar Macrophage Complement-Mediated Phagocytosis of Streptococcus pneumoniae
Cigarette Smoke Exposure Impairs Pulmonary Bacterial Clearance and Alveolar Macrophage Complement-Mediated Phagocytosis of Streptococcus pneumoniae
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DOI：
10.1128/iai.00963-09
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发表时间：
2010-03-01
影响因子：
3.1
通讯作者：
Mancuso, Peter
中科院分区：
文献类型：
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作者：
Phipps, John C.;Aronoff, David M.;Mancuso, Peter
暴露在香烟烟雾中会增加肺炎链球菌引起的肺部和侵袭性感染的风险，肺炎链球菌是社区获得性肺炎患者最常见的分离微生物。尽管存在这种联系，但人们对香烟烟雾暴露降低宿主对肺炎链球菌感染的抵抗力的机制知之甚少。在本研究中，我们比较了BALB/c小鼠在体内暴露于室内空气和香烟烟雾5周后对肺炎链球菌气管内攻击的反应，以及香烟烟雾对肺炎链球菌体外肺泡巨噬细胞吞噬功能的影响。香烟烟雾暴露的小鼠在感染后24和48小时细菌负荷增加，伴随着更明显的临床表现，体温降低，肺组织匀浆细胞因子IL-1β、IL-6、IL-10和肿瘤坏死因子-α(TNF-α)升高。我们还发现，在受到热致死肺炎链球菌攻击后，香烟烟雾暴露的小鼠的支气管肺泡灌洗液中恢复了更多的中性粒细胞。有趣的是，在肺泡巨噬细胞中加入1%香烟烟雾提取物过夜培养，降低了肺炎链球菌的补体介导的吞噬功能，而对未调理的细菌或包被免疫球蛋白的微球的摄取没有影响。这一小鼠模型为香烟烟雾暴露增加肺炎球菌肺炎风险的假设提供了强有力的补充支持，并定义了一种新的细胞机制来帮助解释这种免疫抑制效应。
Cigarette smoke exposure increases the risk of pulmonary and invasive infections caused by Streptococcus pneumoniae, the most commonly isolated organism from patients with community-acquired pneumonia. Despite this association, the mechanisms by which cigarette smoke exposure diminishes host defense against S. pneumoniae infections are poorly understood. In this study, we compared the responses of BALB/c mice following an intratracheal challenge with S. pneumoniae after 5 weeks of exposure to room air or cigarette smoke in a whole-body exposure chamber in vivo and the effects of cigarette smoke on alveolar macrophage phagocytosis of S. pneumoniae in vitro. Bacterial burdens in cigarette smoke-exposed mice were increased at 24 and 48 h postinfection, and this was accompanied by a more pronounced clinical appearance of illness, hypothermia, and increased lung homogenate cytokines interleukin-1 beta (IL-1 beta), IL-6, IL-10, and tumor necrosis factor alpha (TNF-alpha). We also found greater numbers of neutrophils in bronchoalveolar lavage fluid recovered from cigarette smoke-exposed mice following a challenge with heat-killed S. pneumoniae. Interestingly, overnight culture of alveolar macrophages with 1% cigarette smoke extract, a level that did not affect alveolar macrophage viability, reduced complement-mediated phagocytosis of S. pneumoniae, while the ingestion of unopsonized bacteria or IgG-coated microspheres was not affected. This murine model provides robust additional support to the hypothesis that cigarette smoke exposure increases the risk of pneumococcal pneumonia and defines a novel cellular mechanism to help explain this immunosuppressive effect.