Embryonic exposure to ambient concentrations of PFAS impairs the innate immune response in zebrafish and fathead minnow.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants associated with immunotoxicity; however, their effect on innate immune function in fish at ambient concentrations remains unclear. Perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS) are legacy PFAS prevalent in aquatic ecosystems and have been well studied in zebrafish at high concentrations.  The present study evaluated the effects of embryonic exposure (morula through 2 days post hatch) to environmentally relevant concentrations of PFOS or PFHxS (∼0.8-800 ng/L) on the innate immune response of zebrafish (Danio rerio) and fathead minnow (Pimephales promelas). Impacts on the innate immune response were assessed by quantifying neutrophil recruitment and an in vivo respiratory burst. Neutrophil migration was impacted more in fathead minnows, while zebrafish had greater alterations in the respiratory burst. Fathead minnows were more sensitive than zebrafish with respect to the overall response, and PFHxS was slightly more immunotoxic than PFOS. In silico comparison of the peroxisome proliferator-activated receptor (PPARΥ) predicts that the fathead minnow receptor could have a stronger ligand-binding affinity. These findings demonstrate that environmentally- relevant PFHxS or PFOS exposures can suppress innate immune function in a species specific and non-monotonic dose response, potentially increasing susceptibility to pathogen-induced mortality in fish.