Increased Myeloid Cell Production and Lung Bacterial Clearance in Mice Exposed to Cigarette Smoke
Increased Myeloid Cell Production and Lung Bacterial Clearance in Mice Exposed to Cigarette Smoke
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DOI：
10.1165/rcmb.2015-0017oc
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发表时间：
2016-03-01
影响因子：
6.4
通讯作者：
Benarafa, Charaf
中科院分区：
文献类型：
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作者：
Basilico, Paola;Cremona, Tiziana P.;Benarafa, Charaf
肺炎是慢性阻塞性肺疾病（COPD）患者住院的主要原因。虽然大多数COPD患者是吸烟者，但香烟烟雾暴露对肺部细菌病原体清除以及对免疫和炎症反应的影响尚未完全确定。在这里，肺炎链球菌和铜绿假单胞菌的清除和相关的免疫反应进行了检查暴露于香烟烟雾或戒烟后的小鼠。暴露于香烟烟雾6周或4个月的小鼠在暴露后16至24小时感染时，与暴露于空气的小鼠相比，肺细菌负荷降低。当戒烟后进行感染时，先前暴露于烟雾的小鼠的细菌清除动力学逆转到与对照小鼠相当的水平，表明观察到的缺陷不依赖于对烟雾中发现的细菌决定簇的适应性免疫记忆。比较暴露于香烟烟雾的小鼠与从未暴露或戒烟后的小鼠感染前的细胞因子水平和骨髓细胞产生，发现细菌负荷的减少与肺中IL-1 β和粒细胞-巨噬细胞集落刺激因子的较高水平以及骨髓中中性粒细胞储备和单核细胞更新的增加密切相关。使用Serpinb 1a缺陷小鼠与减少中性粒细胞数量和治疗与粒细胞集落刺激因子表明，增加中性粒细胞数量只有助于部分烟雾对感染的影响。我们的研究结果表明，香烟烟雾诱导肺部病原体清除的暂时性和可逆性增加，这与局部炎症和骨髓髓样细胞输出增加相关。
Pneumonia is a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD). Although most patients with COPD are smokers, the effects of cigarette smoke exposure on clearance of lung bacterial pathogens and on immune and inflammatory responses are incompletely defined. Here, clearance of Streptococcus pneumoniae and Pseudomonas aeruginosa and associated immune responses were examined in mice exposed to cigarette smoke or after smoking cessation. Mice exposed to cigarette smoke for 6 weeks or 4 months demonstrated decreased lung bacterial burden compared with air-exposed mice when infected 16 to 24 hours after exposure. When infection was performed after smoke cessation, bacterial clearance kinetics of mice previously exposed to smoke reversed to levels comparable to those of control mice, suggesting that the observed defects were not dependent on adaptive immunological memory to bacterial determinants found in smoke. Comparing cytokine levels and myeloid cell production before infection in mice exposed to cigarette smoke with mice never exposed or after smoke cessation revealed that reduced bacterial burden was most strongly associated with higher levels of IL-1 beta and granulocyte-macrophage colony-stimulating factor in the lungs and with increased neutrophil reserve and monocyte turnover in the bone marrow. Using Serpinb1a-deficient mice with reduced neutrophil numbers and treatment with granulocyte colony-stimulating factor showed that increased neutrophil numbers contribute only in part to the effect of smoke on infection. Our findings indicate that cigarette smoke induces a temporary and reversible increase in clearance of lung pathogens, which correlates with local inflammation and increased myeloid cell output from the bone marrow.