Bacterial extracellular vesicles isolated from organic dust induce neutrophilic inflammation in the lung.
Bacterial extracellular vesicles isolated from organic dust induce neutrophilic inflammation in the lung.
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从有机粉尘中分离出的细菌细胞外囊泡会引起肺部中性粒细胞炎症。
DOI：
10.1152/ajplung.00107.2020
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Boggaram,Vijay
中科院分区：
文献类型：
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作者：
Meganathan,Velmurugan;Moyana,Regina;Natarajan,Kartiga;Kujur,Weshely;Kusampudi,Shilpa;Mulik,Sachin;Boggaram,Vijay
吸入有机粉尘是一种职业危害，可导致呼吸道症状和呼吸道疾病。来自集中动物饲养操作的生物气溶胶富含细菌，并且可能携带可能引起肺部炎症的细菌细胞外囊泡（EV）。目前尚不清楚有机粉尘是否含有细菌EV以及它们是否调节肺部炎症。在此，我们表明，家禽有机粉尘含有诱发肺部炎症的细菌EV（粉尘EV）。用粉尘EV处理气道上皮细胞、THP-1单核细胞和巨噬细胞迅速诱导IL-8、IL-6、ICAM-1、proIL-1β和TNF-α水平。在气道上皮细胞中，炎症介质的诱导是由于mRNA水平增加和NF-κB活化。多粘菌素B不能抑制粉尘EV诱导的炎症介质。用粉尘EV单次和重复治疗小鼠可增加肺KC、IL-6和TNF-α水平，而不显著改变IL-17 A水平。细胞因子的增加与肺中性粒细胞浸润增强相关。用粉尘EV重复治疗小鼠增加了肺平均线性截距，并增加了气道周围的胶原沉积，表明肺重塑。在给药小鼠中还观察到支气管周围细胞浸润和气道上皮增厚。由于细菌EV是纳米尺寸的颗粒，它们可以到达并积聚在细支气管和肺泡区域，导致肺损伤，从而导致呼吸道疾病的发展。我们的研究为有机粉尘中细菌EV的存在及其作为有机粉尘诱导的肺部炎症和肺损伤的病原体之一的作用提供了新的证据。
Inhalation of organic dust is an occupational hazard leading to the development of respiratory symptoms and respiratory diseases. Bioaerosols from concentrated animal feeding operations are rich in bacteria and could carry bacterial extracellular vesicles (EVs) that could induce lung inflammation. It is not known if organic dust contains bacterial EVs and whether they modulate lung inflammation. Herein, we show that poultry organic dust contains bacterial EVs (dust EVs) that induce lung inflammation. Treatment of airway epithelial cells, THP-1-monocytes and -macrophages with dust EVs rapidly induced IL-8, IL-6, ICAM-1, proIL-1β, and TNF-α levels. In airway epithelial cells, induction of inflammatory mediators was due to increased mRNA levels and NF-κB activation. Induction of inflammatory mediators by dust EVs was not inhibited by polymyxin B. Single and repeated treatments of mice with dust EVs increased lung KC, IL-6, and TNF-α levels without significantly altering IL-17A levels. Increases in cytokines were associated with enhanced neutrophil infiltration into the lung. Repeated treatments of mice with dust EVs increased lung mean linear intercept and increased collagen deposition around airways indicating lung remodeling. Peribronchial cell infiltrates and airway epithelial thickening were also observed in treated mice. Because bacterial EVs are nanometer-sized particles, they can reach and accumulate in the bronchiolar and alveolar regions causing lung injury leading to the development of respiratory diseases. Our studies have provided new evidence for the presence of bacterial EVs in organic dust and for their role as one of the causative agents of organic dust-induced lung inflammation and lung injury.