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Tfh cell-mediated impairment of rotavirus-specific antibodies by PAH and PFAS co-exposure in seropositive children
Summary
Two common environmental pollutants, PAHs (found in smoke and car exhaust) and PFAS (used in non-stick cookware and water-resistant fabrics), weaken children's immune responses to rotavirus, a stomach bug that affects millions of kids worldwide. When children are exposed to both pollutants together, their bodies produce fewer protective antibodies against rotavirus, making them more vulnerable to severe illness. This matters because it shows how everyday chemical exposures can undermine vaccines and natural immunity, suggesting we need better protection from these pollutants to keep kids healthy.
Rotavirus (RV) is a major cause of acute gastroenteritis in children, and RV-specific antibodies play a critical role in the intestinal immunity. Circulating T follicular helper (cTfh) cells are essential for generating high quality antigen specific antibodies. However, it remains unclear whether environmental pollutants impair RV-specific antibody responses through Tfh cell-dependent mechanisms. In this study, four urinary PAH metabolites, five plasma PFAS compounds, cTfh cells and their cell subsets, and RV-specific antibodies were measured in children from a known e-waste processing region. Linear regression and Bayesian kernel machine regression (BKMR) analyses were used to examine associations between PAHs and PFAS exposure and RV-specific antibody in seropositive children. Exposure to four PAH metabolites significantly reduced RV-specific IgG levels. 1-OHNap and 2-OHNap levels were negatively correlated with cTfh2 cell frequency, whereas cTfh2 frequency itself was positively correlated with RV-specific IgG levels. Furthermore, five distinct PFAS compounds significantly inhibited cytokine secretion across multiple cTfh cells and cTfh cell subsets. PFHxS exposure specifically impaired RV-specific IgA levels. Notably, co-exposure to PAHs and PFAS suppressed RV-specific IgG levels in a dose-dependent manner. Our findings demonstrate that PAHs and PFASs co-exposure impair cTfh cell function, thereby weakening the immune response against RV infection in children.