PFAS-induced immunotoxicity in freshwater fish of inland China: mechanisms and ecological risks

Per-and polyfluoroalkyl substances (PFAS) are widely distributed across freshwater systems in mainland China, with concentrations showing marked spatial heterogeneity-particularly in eastern regions with intensive industrial activity. Fish not only play a vital ecological role but also serve as an important source of protein for humans. Due to the biomagnification factors (BMF > 1) of PFAS in the food chain, the risk of exposure increases for high-trophic-level fish, other predators, and ultimately humans. Co-exposure with other environmental pollutants further amplifies PFAS-induced immunotoxic effects. The immunotoxicity of PFAS is influenced by carbon chain length and functional groups, with long-chain PFAS and sulfonic acid groups generally exhibiting stronger immunotoxic effects in fish. These compounds significantly suppress both innate and adaptive immune responses by interfering with Toll-like receptor signaling pathways, inducing oxidative stress, and impairing immune cell function. Although current technologies are available for PFAS removal, they still face considerable limitations and challenges. This review summarizes the characteristics and spatial distribution of PFAS contamination in mainland China's aquatic environments and focuses on the mechanisms of PFAS-induced immunotoxicity in fish. It offers valuable insights for future research into the synergistic/antagonistic and time-dependent effects of combined PFAS and multi-pollutant exposure. Moreover, it provides important references for the development of mitigation technologies targeting PFAS-related ecotoxicity in aquatic food chains and for informing relevant policy formulation.