Epidemiological evidence has shown the association between exposure to ambient fine particulate matter (PM) and increased susceptibility to bacterial and viral respiratory infections. However, to date, the underlying mechanisms of immunomodulatory effects of PM remain unclear. Our objective was to explore how exposure to relatively low doses of urban air PM alters innate responses to bacterial and viral stimuli in vitro. We used secondary alveolar epithelial cell line along with monocyte-derived macrophages to replicate innate lung barrier in vitro. Co-cultured cells were first exposed for 24 h to PM_2.5-1 (particle aerodynamic diameter between 1 and 2.5 μm) and subsequently for an additional 24 h to lipopolysaccharide (TLR4), polyinosinic-polycytidylic acid (TLR3), and synthetic single-stranded RNA oligoribonucleotides (TLR7/8) to mimic bacterial or viral stimulation. Toxicological endpoints included pro-inflammatory cytokines (IL-8, IL-6, and TNF-α), cellular metabolic activity, and cell cycle phase distribution. We show that cells exposed to PM_2.5-1 produced higher levels of pro-inflammatory cytokines following stimulation with bacterial TLR4 ligand than cells exposed to PM_2.5-1 or bacterial ligand alone. On the contrary, PM_2.5-1 exposure reduced pro-inflammatory responses to viral ligands TLR3 and TLR7/8. Cell cycle analysis indicated that viral ligands induced cell cycle arrest at the G2-M phase. In PM-primed co-cultures, however, they failed to induce the G2-M phase arrest. Contrarily, bacterial stimulation caused a slight increase in cells in the sub-G1 phase but in PM_2.5-1 primed co-cultures the effect of bacterial stimulation was masked by PM_2.5-1. These findings indicate that PM_2.5-1 may alter responses of immune defense differently against bacterial and viral infections. Further studies are required to explain the mechanism of immune modulation caused by PM in altering the susceptibility to respiratory infections.

流行病学证据表明，暴露于环境细颗粒物（PM）与细菌和病毒性呼吸道感染的易感性之间存在关联。然而，迄今为止，PM的免疫调节作用的潜在机制仍不清楚。我们的目标是探索暴露于相对较低剂量的城市空气PM如何在体外改变对细菌和病毒刺激的先天反应。我们使用次级肺泡上皮细胞系以及单核细胞衍生的巨噬细胞在体外复制先天性肺屏障。首先将共培养的细胞暴露于PM _2.5-1 24小时（空气动力学直径介于1到2.5μm之间），随后再持续24小时，以模拟细菌或病毒刺激，产生脂多糖（TLR4），多肌苷酸聚胞苷酸（TLR3）和合成单链RNA寡核糖核苷酸（TLR7 / 8）。毒理学终点包括促炎细胞因子（IL-8，IL-6和TNF-α），细胞代谢活性和细胞周期阶段分布。我们显示暴露于PM _2.5-1的细胞比细菌暴露于PM _2.5-1或单独细菌配体的细胞产生更高水平的促炎细胞因子，并受到细菌TLR4配体刺激。相反，PM _2.5-1暴露减少了对病毒配体TLR3和TLR7 / 8的促炎反应。细胞周期分析表明，病毒配体诱导了细胞周期停滞在G2-M期。然而，在PM引发的共培养中，它们无法诱导G2-M期停滞。相反，细菌刺激导致亚G1期细胞略有增加，但在PM _2.5-1引发的共培养物中，细菌刺激的作用被PM _2.5-1所掩盖_。这些发现表明，PM _2.5-1可能改变针对细菌和病毒感染的免疫防御反应。需要进一步的研究来解释由PM引起的免疫调节机制在改变对呼吸道感染的敏感性中的作用。