BACKGROUND The World Health Organization estimates that air pollution is responsible for 7 million deaths per annum, with 7% of these attributable to pneumonia. Many of these fatalities have been linked to exposure to high levels of airborne particulates, such as diesel exhaust particles (DEPs). OBJECTIVES We sought to determine whether exposure to DEPs could promote the progression of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae to invasive pneumococcal disease. METHODS We used mouse models and in vitro assays to provide a mechanistic understanding of the link between DEP exposure and pneumococcal disease risk, and we confirmed our findings by using induced sputum macrophages isolated from healthy human volunteers. RESULTS We demonstrate that inhaled exposure to DEPs disrupts asymptomatic nasopharyngeal carriage of S pneumoniae in mice, leading to dissemination to lungs and blood. Pneumococci are transported from the nasopharynx to the lungs following exposure to DEPs, leading to increased proinflammatory cytokine production, reduced phagocytic function of alveolar macrophages, and consequently, increased pneumococcal loads within the lungs and translocation into blood. These findings were confirmed by using DEP-exposed induced sputum macrophages isolated from healthy volunteers, demonstrating that impaired innate immune mechanisms following DEP exposure are also at play in humans. CONCLUSION Lung inhaled DEPs increase susceptibility to pneumococcal disease by leading to loss of immunological control of pneumococcal colonisation, increased inflammation, tissue damage, and systemic bacterial dissemination.

中文翻译：

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暴露于柴油机尾气颗粒会增加对侵袭性肺炎球菌疾病的易感性。

背景 世界卫生组织估计，空气污染每年导致 700 万人死亡，其中 7% 可归因于肺炎。其中许多死亡事件与暴露于高浓度的空气中颗粒物有关，例如柴油机尾气颗粒 (DEP)。目的 我们试图确定暴露于 DEPs 是否可以促进无症状的鼻咽携带肺炎链球菌发展为侵袭性肺炎球菌疾病。方法 我们使用小鼠模型和体外试验来提供对 DEP 暴露与肺炎球菌疾病风险之间联系的机制理解，并且我们通过使用从健康人类志愿者中分离的诱导痰巨噬细胞证实了我们的发现。结果 我们证明，吸入 DEP 会破坏小鼠中肺炎链球菌的无症状鼻咽携带，导致传播到肺部和血液。肺炎球菌在暴露于 DEP 后从鼻咽转运到肺部，导致促炎细胞因子产生增加，肺泡巨噬细胞的吞噬功能降低，从而增加肺内的肺炎球菌负荷并转移到血液中。这些发现通过使用从健康志愿者中分离的暴露于 DEP 的诱导痰巨噬细胞得到证实，表明暴露于 DEP 后受损的先天免疫机制也在人类中起作用。结论 肺吸入 DEPs 通过导致肺炎球菌定植的免疫控制丧失、炎症增加、