Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome
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....
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| Published in | Nature communications Vol. 12; no. 1; pp. 2915 - 17 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
18.05.2021
Nature Publishing Group Nature Portfolio |
| Subjects | |
| Online Access | Get full text |
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| 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
2+
-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.
The double-stranded DNA receptor AIM2 is able to sense the environmental pollutant perfluorooctane sulfonate, a prototypical perfluoro-alkyl substrate. Activation of the AIM2 pathway leads to inflammation and tissue damage via IL-1β secretion and pyroptosis of affected innate immune cells. |
|---|---|
| AbstractList | 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
2+
-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.
The double-stranded DNA receptor AIM2 is able to sense the environmental pollutant perfluorooctane sulfonate, a prototypical perfluoro-alkyl substrate. Activation of the AIM2 pathway leads to inflammation and tissue damage via IL-1β secretion and pyroptosis of affected innate immune cells. 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 2+ -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. 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 Ca2+-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.The double-stranded DNA receptor AIM2 is able to sense the environmental pollutant perfluorooctane sulfonate, a prototypical perfluoro-alkyl substrate. Activation of the AIM2 pathway leads to inflammation and tissue damage via IL-1β secretion and pyroptosis of affected innate immune cells. 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 Ca2+-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.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 Ca2+-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. 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. The double-stranded DNA receptor AIM2 is able to sense the environmental pollutant perfluorooctane sulfonate, a prototypical perfluoro-alkyl substrate. Activation of the AIM2 pathway leads to inflammation and tissue damage via IL-1β secretion and pyroptosis of affected innate immune cells. |
| ArticleNumber | 2915 |
| Author | Ye, Xiao-Yan Wang, Li-Qiu Zheng, Yan-Yan Li, Chun-Wei Cui, Jun She, Yuan-Chu Li, Li-Yue Zhao, Zhi-Yao Dong, Guang-Hui Yang, Shuai Sun, Lin Liu, Tao Bao, Qing |
| Author_xml | – sequence: 1 givenname: Li-Qiu surname: Wang fullname: Wang, Li-Qiu organization: MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University – sequence: 2 givenname: Tao surname: Liu fullname: Liu, Tao organization: MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University – sequence: 3 givenname: Shuai surname: Yang fullname: Yang, Shuai organization: MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University – sequence: 4 givenname: Lin surname: Sun fullname: Sun, Lin organization: Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University – sequence: 5 givenname: Zhi-Yao surname: Zhao fullname: Zhao, Zhi-Yao organization: MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University – sequence: 6 givenname: Li-Yue surname: Li fullname: Li, Li-Yue organization: Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University – sequence: 7 givenname: Yuan-Chu surname: She fullname: She, Yuan-Chu organization: MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University – sequence: 8 givenname: Yan-Yan surname: Zheng fullname: Zheng, Yan-Yan organization: MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University – sequence: 9 givenname: Xiao-Yan surname: Ye fullname: Ye, Xiao-Yan organization: Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University – sequence: 10 givenname: Qing surname: Bao fullname: Bao, Qing organization: Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University – sequence: 11 givenname: Guang-Hui orcidid: 0000-0002-2578-3369 surname: Dong fullname: Dong, Guang-Hui organization: Guangdong Provincial Engineering Technology Research Center of Environmental Pollution and Health Risk Assessment, Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University – sequence: 12 givenname: Chun-Wei surname: Li fullname: Li, Chun-Wei email: hi_chunwei@aliyun.com organization: Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University – sequence: 13 givenname: Jun orcidid: 0000-0002-8000-3708 surname: Cui fullname: Cui, Jun email: cuij5@mail.sysu.edu.cn organization: MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34006824$$D View this record in MEDLINE/PubMed |
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| DOI | 10.1038/s41467-021-23201-0 |
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| Snippet | Perfluoroalkyl substances (PFAS) are widely used in various manufacturing processes. Accumulation of these chemicals has adverse effects on human health,... The double-stranded DNA receptor AIM2 is able to sense the environmental pollutant perfluorooctane sulfonate, a prototypical perfluoro-alkyl substrate.... |
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| Title | Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome |
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