Aryl hydrocarbon receptor activation differentially impacts Cholera toxin-specific IgA levels in feces and serum of male and female mice

Abstract

Abstract Secretory IgA plays a critical role in neutralizing enteric toxins and protecting against some intestinal pathogens. In mice, activation of the aryl hydrocarbon receptor (AhR) with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to suppress antigen-specific systemic IgM and IgG responses, whereas the impact of AhR activation on mucosal IgA responses is less clear. Previous studies in our laboratory have demonstrated that Cholera toxin (CT)-specific fecal IgA levels in female mice are initially suppressed by TCDD exposure, but they recover to control levels within three weeks, unlike serum IgA levels. The goal of this study was to determine if TCDD exposure similarly alters CT-specific IgA levels in male mice. Male and female C57Bl/6 mice were administered peanut oil (vehicle) or TCDD on day 0, and each animal was immunized with CT (10 μg/Kg) on days 1, 8 and 15. Feces were collected on days 14 and 21, and antibody levels were measured by ELISA. Relative to controls at week 2, CT-specific fecal IgA levels were significantly decreased (P ≤ 0.05) by TCDD exposure at 40 μg/Kg (but not lower doses) in both male and female mice. Suppressed antibody levels persisted at 3 weeks in male mice only. In serum, significant suppression of CT-specific IgA was observed at week 3 in male mice (40 μg/Kg TCDD) and at week 4 in female mice (10 and 40 μg/Kg TCDD). These results suggest that antigen-specific fecal IgA responses in female mice recover from AhR-mediated suppression more rapidly than systemic responses and more rapidly than in male mice.