Developmental exposure to a PFAS mixture impairs the anamnestic response to influenza A virus infection in mice

Developmental exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to reduced antibody responses to childhood vaccines, but the underlying mechanisms remain unclear. Antibody production relies on interactions between various immune cell types, and it is unknown which are affected by PFAS exposure during development. To investigate this in a human-health relevant system, an in vivo model was established to delineate effects of developmental exposure to a mixture of four PFAS commonly found in human serum: PFOA, PFOS, PFHxS, and PFNA. Pregnant mice consumed water containing these PFAS throughout gestation and lactation. PFAS were measured in both mothers and offspring, and an exposure that avoided overt health issues was selected. The immune response to influenza A virus (IAV) infection was assessed in male and female offspring. Results showed that developmental PFAS exposure reduced IAV-specific antibody levels in both sexes. However, it diminished T follicular helper cells and germinal center B cells--critical for antibody production--in only female offspring. These findings highlight possible sex-specific immune effects and identify potential cellular mechanisms behind reduced antibody levels. Since these immune cells are essential for antibody production in humans, this study provides valuable insights into how PFAS exposure may impact human health. SynopsisA novel mouse model of developmental exposure to a human-relevant PFAS mixture recapitulates observations in epidemiological studies and also provides new insight into potential mechanisms of the lower antibody levels observed in humans.