Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome

By Li-Qiu Wang, Tao Liu, Shuai Yang, Lin Sun, Zhi-Yao Zhao, Li-Yue Li, Yuan-Chu She, Yan-Yan Zheng, Xiao-Yan Ye, Qing Bao, Guang-Hui Dong, Chun-Wei Li, and Jun Cui
Nat Commun
May 25, 2021
DOI: 10.1038/s41467-021-23201-0

Perfluoroalkyl substances (PFAS) are widely used in various manufacturing processes. Accumulation of these chemicals has adverse effects on human health, including inflammation in multiple organs, yet how PFAS are sensed by host cells, and how tissue inflammation eventually incurs, is still unclear. Here, we show that the double-stranded DNA receptor AIM2 is able to recognize perfluorooctane sulfonate (PFOS), a common form of PFAS, to trigger IL-1β secretion and pyroptosis. Mechanistically, PFOS activates the AIM2 inflammasome in a process involving mitochondrial DNA release through the Ca-PKC-NF-κB/JNK-BAX/BAK axis. Accordingly, Aim2 mice have reduced PFOS-induced inflammation, as well as tissue damage in the lungs, livers, and kidneys in both their basic condition and in an asthmatic exacerbation model. Our results thus suggest a function of AIM2 in PFOS-mediated tissue inflammation, and identify AIM2 as a major pattern recognition receptor in response to the environmental organic pollutants.

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