Maternal tolerance achieved during pregnancy is transferred to the offspring via breast milk and persistently protects the offspring from allergic asthma

Abstract

Maternal, more than paternal, asthma is a risk factor for the development of asthma in children. Recently, epidemiologic studies have shown that environmental exposures during pregnancy might influence the development of childhood asthma and allergies. The aim of the present study was to investigate whether the induction of tolerance against a specific antigen during pregnancy prevents in the offspring the development of allergic asthma in response to this antigen. Balb/c mice were orally tolerized with ovalbumin (OVA) during pregnancy. The offspring of tolerized and naïve mothers were immunized with OVA at 6 weeks and 4 months of age and analysed in our murine asthma model. While the offspring of naïve mice developed increased AHR, eosinophilic airway inflammation, T-helper type 2 cytokine production and high serum IgE levels in response to OVA sensitization, the offspring of tolerized mice were almost completely protected from asthma, even when immunized as late as 4 months after birth. Breastfeeding was crucial for protection because tolerance was only observed when the offspring were nursed by their own mothers and not when nursed by naïve wet-nurses. Allergen-specific IgG(1) antibodies were exclusively increased in the breast milk of tolerant mothers and serum of protected pups, indirectly supporting its important role in tolerance transfer from the mother to the offspring. Sensitization of the F1 generation from OVA-tolerized mothers with a heterologous allergen enhanced the immune response to this antigen. Our results demonstrate that mucosal allergen contact during pregnancy modifies the asthma and allergy risk of the offspring mediated via breast milk. This observation may suggest that the time window for primary prevention strategies starts even before early childhood during pregnancy.