Per- and polyfluoroalkyl substances alter innate immune function: evidence and data gaps

Abstract

Per- and polyfluoroalkyl substances (PFASs) are a large class of compounds used in a variety of processes and consumer products. Their unique chemical properties make them ubiquitous and persistent environmental contaminants while also making them economically viable and socially convenient. To date, several reviews have been published to synthesize information regarding the immunotoxic effects of PFASs on the adaptive immune system. However, these reviews often do not include data on the impact of these compounds on innate immunity. Here, current literature is reviewed to identify and incorporate data regarding the effects of PFASs on innate immunity in humans, experimental models, and wildlife. Known mechanisms by which PFASs modulate innate immune function are also reviewed, including disruption of cell signaling, metabolism, and tissue-level effects. For PFASs where innate immune data are available, results are equivocal, raising additional questions about common mechanisms or pathways of toxicity, but highlighting that the innate immune system within several species can be perturbed by exposure to PFASs. Recommendations are provided for future research to inform hazard identification, risk assessment, and risk management practices for PFASs to protect the immune systems of exposed organisms as well as environmental health.

Keywords:

• Per- and polyfluoroalkyl substances
• PFAS
• innate immunity
• ecotoxicology
• zebrafish
• immunotoxicology

Acknowledgements

The Authors apologize to those colleagues whose work could not be cited because of space limitations. Note: portions of this manuscript were included as part of DWP doctoral dissertation (Phelps 2022).

Disclosure statement

DWP was paid consulting fees by the Center for Environmental Health (Oakland, CA), for consulting regarding a petition for testing of certain PFAS (May 2019–August 2022) as well as to provide toxicological expertise regarding the PFAS detected in fluorinated high-density polyethylene (March–May 2023). DWP was also paid to provide literature support to JCD for a PFAS expert witness report (May 2023). JCD serves/has served as a plaintiff’s expert witness for several cases involving PFAS manufacturers. All other authors declare no competing interests relevant to the content of this article.

Additional information

Funding

This work was supported by was supported by the National Institute of Environmental Health Sciences (NIEHS) of the United States National Institutes of Health (NIH) (P42-ES031009 to JCD and JAY; R03-ES032532 to JAY) and the North Carolina State University Center for Human Health and the Environment (NIH P30-ES025128 to JAY). DWP was supported by a NIH Biotechnology Traineeship (T32-GM008776). AMC was supported by a fellowship from the North Carolina State University Genetics & Genomics Scholars program and by the North Carolina State University Toxicology Program training grant (NIEHS T32-ES007046). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.