Air pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence of neurodegenerative diseases such as Alzheimer’s disease. Inhaled components of PM may directly invade the brain via the olfactory route, or act through peripheral system responses resulting in inflammation and oxidative stress in the brain. Microglia are the immune cells of the brain implicated in the progression of neurodegenerative diseases. However, it remains unknown how PM affects live human microglia. Here we show that two different PMs derived from exhausts of cars running on EN590 diesel or compressed natural gas (CNG) alter the function of human microglia-like cells in vitro. We exposed human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGLs) to traffic related PMs and explored their functional responses. Lower concentrations of PMs ranging between 10 and 100 µg ml−1 increased microglial survival whereas higher concentrations became toxic over time. Both tested pollutants impaired microglial phagocytosis and increased secretion of a few proinflammatory cytokines with distinct patterns, compared to lipopolysaccharide induced responses. iMGLs showed pollutant dependent responses to production of reactive oxygen species (ROS) with CNG inducing and EN590 reducing ROS production. Our study indicates that traffic-related air pollutants alter the function of human microglia and warrant further studies to determine whether these changes contribute to adverse effects in the brain and on cognition over time. This study demonstrates human iPSC-microglia as a valuable tool to study functional microglial responses to environmental agents.

中文翻译：

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汽车尾气中的颗粒物改变了人类 iPSC 衍生的小胶质细胞的功能

空气污染被认为是神经系统疾病的一个新兴环境风险因素。大规模流行病学研究将交通相关颗粒物 (PM) 与认知功能受损和阿尔茨海默病等神经退行性疾病发病率增加联系起来。吸入的 PM 成分可能通过嗅觉途径直接侵入大脑，或通过周围系统反应起作用，导致大脑炎症和氧化应激。小胶质细胞是大脑的免疫细胞，与神经退行性疾病的进展有关。然而，PM 如何影响活的人类小胶质细胞仍不清楚。在这里，我们展示了来自使用 EN590 柴油或压缩天然气 (CNG) 的汽车尾气的两种不同的 PM，在体外改变了人类小胶质细胞样细胞的功能。我们将人类诱导多能干细胞 (iPSC) 衍生的小胶质细胞样细胞 (iMGL) 暴露于交通相关的 PM 中，并探索它们的功能反应。 10 至 100 µg ml−1 之间的较低浓度 PM 会增加小胶质细胞的存活率，而较高浓度会随着时间的推移而变得有毒。与脂多糖诱导的反应相比，两种测试的污染物都会损害小胶质细胞的吞噬作用，并增加一些具有不同模式的促炎细胞因子的分泌。 iMGL 显示出对活性氧 (ROS) 产生的污染物依赖性反应，其中 CNG 诱导且 EN590 减少 ROS 产生。我们的研究表明，与交通相关的空气污染物会改变人类小胶质细胞的功能，并需要进一步研究以确定这些变化是否会随着时间的推移对大脑和认知产生不利影响。这项研究证明人类 iPSC 小胶质细胞是研究功能性小胶质细胞对环境因素反应的宝贵工具。