Abstract
BackgroundThe mechanism(s) responsible for the reduced risk of allergic disease in breastfed infants are not fully understood. Using an established murine model of asthma, we demonstrated previously that resistance to allergic airway disease transmitted from allergic mothers to breastfed offspring requires maternal B cell-derived factors.ObjectiveThe aim of this study was to investigate the role of offspring neonatal Fc receptor for IgG uptake by intestinal epithelial cells (FcRn) in this breast milk transferred protection from allergy.MethodsAllergic airway disease was induced during pregnancy in C57BL/6 female mice. These allergic mothers foster nursed naive FcRn+/- or FcRn-/- progeny born to FcRn+/- females that were mated to C57BL/6J-FcRn-/- male mice. In offspring deficient in FcRn, we expected reduced levels of systemic allergen-specific IgG1, a consequence of decreased absorption of maternal IgG from the lumen of the neonatal gastrointestinal tract. Using this model, we were able to investigate how breast milk IgG affected offspring responses to allergic sensitization.ResultsLevels of maternal antibodies absorbed from the breast milk of allergic foster mothers were determined in weanling FcRn-sufficient or -deficient mice. Maternal transmission of allergen-specific IgG1 to breastfed FcRn-/- offspring was at levels 103-104 lower than observed in FcRn+/- or FcRn+/+ mice. Five weeks after weaning, when offspring were 8 wk old, mice were sensitized and challenged to evaluate their susceptibility to develop allergic airway disease. Protection, indicated by reduced parameters of disease (allergen-specific IgE in serum, eosinophilic inflammation in the airways and lung) were evident in FcRn-sufficient mice nursed as neonates by allergic mothers. In contrast, FcRn-deficient mice breastfed by the same mothers acquired limited, if any, protection from development of allergen-specific IgE and associated pathology.ConclusionsFcRn expression was a major factor in determining how breastfed offspring of allergic mothers acquired levels of systemic allergen-specific IgG1 sufficient to inhibit allergic sensitization in this model.
Highlights
The mechanism(s) responsible for the reduced risk of allergic disease in breastfed infants are not fully understood
We demonstrated that the breast milk from allergic mothers can protect offspring from ovalbumin (OVA)induced airway disease (AAD); with the protective effect dependent on intact maternal B cell immunity [28]
FcRn-deficient mice were susceptible to OVA-induced AAD Prior to performing adoptive nursing studies to elucidate the role of ingested maternal allergen-specific IgG1 in protecting offspring from AAD, it was necessary to determine whether wildtype and FcRn-/- mice developed comparable parameters of allergic disease
Summary
The mechanism(s) responsible for the reduced risk of allergic disease in breastfed infants are not fully understood. Using an established murine model of asthma, we demonstrated previously that resistance to allergic airway disease transmitted from allergic mothers to breastfed offspring requires maternal B cell-derived factors. The human fetus acquires a substantial amount of maternal IgG in utero, transported across the placenta by the neonatal Fc receptor (FcRn) [8]. In both humans and rodents, maternal IgG is acquired from breast milk [9,10], absorbed from the gut lumen via FcRn-dependent transcytosis in intestinal epithelial cells [11,12,13,14]. The structure of FcRn is well characterized [12,20] and several studies demonstrate a dynamic role of this receptor beyond the neonatal period [21,22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
