2. Academic Validation
  3. Poly- and Perfluoroalkyl Substances Induce Immunotoxicity via the TLR Pathway in Zebrafish: Links to Carbon Chain Length

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

  • Environ Sci Technol. 2023 Apr 5. doi: 10.1021/acs.est.2c09716.
Liang Tang 1,  Wenhui Qiu 2,  Shuwen Zhang 2,  Jiazhen Wang 2,  Xin Yang 3,  Bentuo Xu 4,  Jason T Magnuson 5,  Elvis Genbo Xu 6,  Minghong Wu 1,  Chunmiao Zheng 2 7
Affiliations

Affiliations

  • 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, 1088 Xueyuan Avenue, Nanshan District, Shenzhen 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, 1088 Xueyuan Avenue, Nanshan District, Shenzhen 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, Chashan University Town, Wenzhou 325035, China.
  • 5 Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Måltidets Hus - Richard Johnsens gate 4, Stavanger 4021, Norway.
  • 6 Department of Biology, University of Southern Denmark, Campusvej 55, Odense 5230, Denmark.
  • 7 EIT Institute for Advanced Study, 568 Tongxin Road, Zhenhai District, Ningbo 315410, China.
PMID: 37017313 DOI: 10.1021/acs.est.2c09716
Abstract

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.

Keywords

PFASs; TLR pathway; carbon chain length; immunotoxicity; zebrafish.

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