Perfluoroalkyl Substance Pollutants Activate the Innate Immune System Through the AIM2 Inflammasome

Overview

Journal Nat Commun

Specialty Biology

Date 2021 May 19

PMID 34006824

Citations 41

Authors

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

Jun Cui

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Evidence of the occurrence, detection, and ecotoxicity studies of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in aqueous environments.

Omotola E, Ohoro C, Amaku J, Conradie J, Olisah C, Akpomie K J Environ Health Sci Eng. 2025; 23(1):10.

PMID: 40018265 PMC: 11861503. DOI: 10.1007/s40201-025-00934-4.

GSDMD-mediated pyroptosis: molecular mechanisms, diseases and therapeutic targets.

Li Y, Guo B Mol Biomed. 2025; 6(1):11.

PMID: 39994107 PMC: 11850691. DOI: 10.1186/s43556-025-00249-8.

Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders.

Zhang G, Wei H, Zhao A, Yan X, Zhang X, Gan J J Neuroinflammation. 2025; 22(1):34.

PMID: 39920753 PMC: 11806845. DOI: 10.1186/s12974-025-03363-0.

Increased perfluorooctanoic acid accumulation facilitates the migration and invasion of lung cancer cells via remodeling cell mechanics.

Mei J, Jiang J, Li Z, Pan Y, Xu K, Gao X Proc Natl Acad Sci U S A. 2024; 121(51):e2408575121.

PMID: 39665760 PMC: 11665856. DOI: 10.1073/pnas.2408575121.

Pyroptosis in asthma: inflammatory phenotypes, immune and non-immune cells, and novel treatment approaches.

Hao Y, Wang W, Zhang L, Li W Front Pharmacol. 2024; 15:1452845.

PMID: 39611173 PMC: 11603363. DOI: 10.3389/fphar.2024.1452845.

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