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-kB 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. Peri-bronchial 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

中文翻译：

---

从有机粉尘中分离出的细菌细胞外囊泡诱导肺中性粒细胞炎症

吸入有机粉尘是一种职业危害，会导致呼吸道症状和呼吸道疾病的发展。来自动物集中饲养操作的生物气溶胶含有丰富的细菌，并且可能携带可诱发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 以及它们是否会调节肺部炎症。在此，我们展示了家禽有机粉尘含有诱导肺部炎症的细菌 EV（粉尘 EV）。用灰尘 EV 处理气道上皮细胞、THP-1-单核细胞和-巨噬细胞可迅速诱导 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-kB 激活。灰尘 EV 对炎症介质的诱导不受多粘菌素 B 的抑制。用灰尘 EV 对小鼠进行单次和重复治疗会增加肺 KC、IL-6 和 TNF-α 水平，而没有显着改变 IL-17A 水平。细胞因子的增加与中性粒细胞浸润肺的增强有关。用灰尘 EV 重复治疗小鼠会增加肺平均线性截距和增加气道周围胶原蛋白沉积，表明肺重塑。在治疗的小鼠中也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，导致呼吸系统疾病的发展。