Per- and polyfluoroalkyl substances alter innate immune function: evidence and data gaps

Per- and polyfluoroalkyl substances (PFASs) are a large class of compounds used in a variety of processes and consumer products. Their unique chemical properties make them ubiquitous and persistent environmental contaminants while also making them economically viable and socially convenient. To date, several reviews have been published to synthesize information regarding the immunotoxic effects of PFASs on the adaptive immune system. However, these reviews often do not include data on the impact of these compounds on innate immunity. Here, current literature is reviewed to identify and incorporate data regarding the effects of PFASs on innate immunity in humans, experimental models, and wildlife. Known mechanisms by which PFASs modulate innate immune function are also reviewed, including disruption of cell signaling, metabolism, and tissue-level effects. For PFASs where innate immune data are available, results are equivocal, raising additional questions about common mechanisms or pathways of toxicity, but highlighting that the innate immune system within several species can be perturbed by exposure to PFASs. Recommendations are provided for future research to inform hazard identification, risk assessment, and risk management practices for PFASs to protect the immune systems of exposed organisms as well as environmental health.

全氟和多氟烷基物质（Per- and polyfluoroalkyl substances, PFASs）是一类应用于多种工业流程与消费品的庞大化合物家族。其独特的化学特性使其成为无处不在且持久存在的环境污染物，同时也赋予其经济实用性与社会使用便利性。迄今为止，已有多篇综述文献对PFASs针对适应性免疫系统的免疫毒性相关信息进行了综合归纳。不过，此类综述往往未涵盖这类化合物对先天免疫系统的影响相关数据。本文通过梳理当前已发表的文献，整合并分析PFASs对人类、实验模型生物以及野生动物先天免疫系统的影响相关数据；同时，本文还综述了PFASs调控先天免疫功能的已知机制，包括细胞信号通路干扰、代谢紊乱以及组织层面的效应。针对已有先天免疫相关研究数据的PFASs而言，现有研究结果尚存争议，这为探明其共同毒性机制或通路带来了更多疑问，但也凸显出多个物种的先天免疫系统可因PFASs暴露而受到扰动。本文为未来研究提出相关建议，以期为PFASs的危害识别、风险评估与风险管理实践提供参考，进而保护暴露生物体的免疫系统健康与环境健康。