Abstract：
Community-acquired pneumonia remains a major contributor to global communicable disease-mediated mortality. Neutrophils play a leading role in trying to contain bacterial lung infection, but they also drive detrimental pulmonary inflammation, when dysregulated. Here we aimed at understanding the role of microRNA-223 in orchestrating pulmonary inflammation during pneumococcal pneumonia. Serum microRNA-223 was measured in patients with pneumococcal pneumonia and in healthy subjects. Pulmonary inflammation in wild-type and microRNA-223-knockout mice was assessed in terms of disease course, histopathology, cellular recruitment and evaluation of inflammatory protein and gene signatures following pneumococcal infection. Low levels of serum microRNA-223 correlated with increased disease severity in pneumococcal pneumonia patients. Prolonged neutrophilic influx into the lungs and alveolar spaces was detected in pneumococci-infected microRNA-223-knockout mice, possibly accounting for aggravated histopathology and acute lung injury. Expression of microRNA-223 in wild-type mice was induced by pneumococcal infection in a time-dependent manner in whole lungs and lung neutrophils. Single-cell transcriptome analyses of murine lungs revealed a unique profile of antimicrobial and cellular maturation genes that are dysregulated in neutrophils lacking microRNA-223. Taken together, low levels of microRNA-223 in human pneumonia patient serum were associated with increased disease severity, whilst its absence provoked dysregulation of the neutrophil transcriptome in murine pneumococcal pneumonia.
摘要：
社区获得性肺炎仍然是全球传染病介导死亡率的主要原因。嗜中性粒细胞在试图遏制细菌性肺部感染中起着主导作用，但它们也会引发有害的肺部炎症，当失调时。在这里，我们旨在了解microRNA-223在肺炎球菌肺炎期间协调肺部炎症中的作用。在肺炎球菌肺炎患者和健康受试者中测量血清microRNA-223。根据病程评估野生型和microRNA-223敲除小鼠的肺部炎症，组织病理学,肺炎球菌感染后的细胞募集以及炎性蛋白和基因特征的评估。低水平的血清microRNA-223与肺炎球菌肺炎患者的疾病严重程度增加相关。在肺炎球菌感染的microRNA-223敲除小鼠中检测到持续的嗜中性粒细胞流入肺和肺泡腔，可能导致组织病理学加重和急性肺损伤。肺炎球菌感染以时间依赖性方式在全肺和肺嗜中性粒细胞中诱导野生型小鼠中microRNA-223的表达。鼠肺的单细胞转录组分析揭示了在缺乏microRNA-223的嗜中性粒细胞中失调的抗微生物和细胞成熟基因的独特特征。一起来看,人肺炎患者血清中低水平的microRNA-223与疾病严重程度增加有关，而它的缺失会引起鼠肺炎球菌肺炎中性粒细胞转录组的失调。
