Poly- and Perfluoroalkyl Substances Induce Immunotoxicity via the TLR Pathway in Zebrafish: Links to Carbon Chain Length

Tang，Liang1; Qiu，Wenhui2; Zhang，Shuwen2; Wang，Jiazhen2; Yang，Xin3; Xu，Bentuo4; Magnuson，Jason T.5; Xu，Elvis Genbo6; Wu，Minghong1; Zheng，Chunmiao2,7

2022

10.1021/acs.est.2c09716

Environmental Science and Technology   Impact Factor & Quartile

0013-936X

1520-5851

Previous studies have reported the immunotoxicity of per- and polyfluoroalkyl substances (PFASs), but it remains a significant challenge to assess over 10,000 distinct PFASs registered in the distributed structure-searchable toxicity (DSSTox) database. We aim to reveal the mechanisms of immunotoxicity of different PFASs and hypothesize that PFAS immunotoxicity is dependent on the carbon chain length. Perfluorobutanesulfonic acid (PFBA), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) representing different carbon chain lengths (4-9) at environmentally relevant levels strongly reduced the host’s antibacterial ability during the zebrafish’s early-life stage. Innate and adaptive immunities were both suppressed after PFAS exposures, exhibiting a significant induction of macrophages and neutrophils and expression of immune-related genes and indicators. Interestingly, the PFAS-induced immunotoxic responses were positively correlated to the carbon chain length. Moreover, PFASs activated downstream genes of the toll-like receptor (TLR), uncovering a seminal role of TLR in PFAS immunomodulatory effects. Myeloid differentiation factor 88 (MyD88) morpholino knock-down experiments and MyD88 inhibitors alleviated the immunotoxicity of PFASs. Overall, the comparative results demonstrate differences in the immunotoxic responses of PFASs due to carbon chain length in zebrafish, providing new insights into the prediction and classification of PFASs mode of toxic action based on carbon chain length.

carbon chain length immunotoxicity PFASs TLR pathway zebrafish

English

Corresponding

2-s2.0-85152127009

Scopus

1.Key Laboratory of Organic Compound Pollution Control Engineering (MOE),School of Environmental and Chemical Engineering,Shanghai University,Shanghai,200444,China
2.Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control,School of Environmental Science and Engineering,Southern University of Science and Technology,Shenzhen,1088 Xueyuan Avenue,518055,China
3.Shenzhen Key Laboratory of Precision Measurement and Early Warning Technology for Urban Environmental Health Risks,School of Environmental Science and Engineering,Southern University of Science and Technology,Shenzhen,1088 Xueyuan Avenue,518055,China
4.National and Local Joint Engineering Research Center of Ecological Treatment Technology for Urban Water Pollution,School of Life and Environmental Science,Wenzhou University,Wenzhou,Chashan University Town,325035,China
5.Department of Chemistry,Bioscience and Environmental Engineering,University of Stavanger,Stavanger,Måltidets Hus - Richard Johnsens gate 4,4021,Norway
6.Department of Biology,University of Southern Denmark,Odense,Campusvej 55,5230,Denmark
7.EIT Institute for Advanced Study,Ningbo,568 Tongxin Road,315410,China

Tang，Liang,Qiu，Wenhui,Zhang，Shuwen,et al. Poly- and Perfluoroalkyl Substances Induce Immunotoxicity via the TLR Pathway in Zebrafish: Links to Carbon Chain Length[J]. Environmental Science and Technology,2022.

Tang，Liang.,Qiu，Wenhui.,Zhang，Shuwen.,Wang，Jiazhen.,Yang，Xin.,...&Zheng，Chunmiao.(2022).Poly- and Perfluoroalkyl Substances Induce Immunotoxicity via the TLR Pathway in Zebrafish: Links to Carbon Chain Length.Environmental Science and Technology.

Tang，Liang,et al."Poly- and Perfluoroalkyl Substances Induce Immunotoxicity via the TLR Pathway in Zebrafish: Links to Carbon Chain Length".Environmental Science and Technology (2022).