Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University and Shanghai Respiratory Research Institute, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.
Department of Infectious Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.
Respir Res. 2018 Jan 8;19(1):5. doi: 10.1186/s12931-017-0700-0.
Epidemiological studies have shown that urban particulate matter (PM) increases the risk of respiratory infection. However, the underlying mechanisms are poorly understood. PM has been postulated to suppress the activation of airway epithelial innate defence in response to infection.
The effects of PM on antibacterial defence were studied using an in vitro infection model. The levels of antimicrobial peptides were measured using RT-PCR and ELISA. In addition to performing colony-forming unit counts and flow cytometry, confocal microscopy was performed to directly observe bacterial invasion upon PM exposure.
We found that PM PM increased bacterial invasion by impairing the induction of β-defensin-2 (hBD-2), but not the other antimicrobial peptides (APMs) secreted by airway epithelium. PM further increases bacteria-induced ROS production, which is accompanied by an accelerated cell senescence and a decrease in bacteria-induced hBD-2 production, and the antioxidant NAC treatment attenuates these effects. The PM exposure further upregulated the expression of IL-8 but downregulated the expression of IL-13 upon infection.
PM promotes bacterial invasion of airway epithelial cells by attenuating the induction of hBD-2 via an oxidative burst. These findings associate PM with an increased susceptibility to infection. These findings provide insight into the underlying mechanisms regarding the pathogenesis of particulate matter.
流行病学研究表明，城市颗粒物（PM）会增加呼吸道感染的风险。然而，其潜在机制尚不清楚。PM 被认为会抑制气道上皮固有防御系统在感染时的激活。
本研究使用体外感染模型来研究 PM 对抗菌防御的影响。采用 RT-PCR 和 ELISA 法检测抗菌肽水平。除了进行菌落形成单位计数和流式细胞术外，还进行了共聚焦显微镜检查，以直接观察 PM 暴露后细菌的入侵情况。
我们发现，PM 通过损害β-防御素-2（hBD-2）的诱导，而不是气道上皮细胞分泌的其他抗菌肽（APMs），增加了细菌的入侵。PM 进一步增加细菌诱导的 ROS 产生，这伴随着细胞衰老的加速和细菌诱导的 hBD-2 产生的减少，抗氧化剂 NAC 处理可减弱这些作用。PM 暴露进一步上调了感染时的 IL-8 表达，但下调了 IL-13 的表达。
PM 通过氧化爆发削弱 hBD-2 的诱导，从而促进气道上皮细胞中细菌的入侵。这些发现将 PM 与感染易感性增加联系起来。这些发现为颗粒物发病机制的潜在机制提供了深入的了解。
