Potential effects of PFAS exposure on trained immunity: From mechanisms to health risks

Abstract

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants that are widely used in industry and consumption due to their unique chemical properties, but their extreme persistence and bioaccumulation potential pose significant risks to human health. There is growing evidence that PFAS exposure may disrupt trained immunity—a novel form of innate immune memory driven by epigenetic and metabolic reprogramming—thereby enhancing immune responses upon re-exposure to pathogens. While the immunotoxic effects of PFAS have been extensively studied in the context of adaptive immunity, their impact on trained immunity represents a groundbreaking and underexplored area of research. This study reviews recent studies on the effects of PFAS exposure on the innate immune system, evaluating the mechanisms by which PFAS disrupt trained immunity through epigenetic regulation and metabolic reprogramming, and the emerging evidence suggesting potential links between PFAS-induced dysregulation of trained immunity and autoimmune pathogenesis and chronic inflammation. Given the environmental persistence and widespread distribution of PFAS, further mechanistic research is essential to elucidate their immunotoxic effects on human health, which will be critical for developing targeted prevention strategies and informing evidence-based regulatory decisions.