Maternal control of dietary and gut microbial antigen exposure promotes enhanced tolerance and prevents allergic responses

Abstract

Abstract The incidence of allergic disorders is rapidly increasing in children in Western societies, and is linked to allergen avoidance diets and decreased exposure to microbes and microbial antigens in early life. Exposure to dietary antigens and the microbiota via the gastrointestinal tract early in life is associated with a reduced risk of allergic disorders, however the optimal time to introduce these antigens, where the immune system encounters these antigens, and what controls the immune systems exposure to define this time in early life is largely unknown. We identified a window of time in early life in which luminal antigens are shunted to the colonic lamina propria (LP) immune system to induce enhanced tolerogenic responses. Delivery of luminal antigens to the colonic immune system during this time in life was mediated by the formation of goblet cell-associated antigen passages (GAPs), which were regulated by goblet cell (GC) intrinsic sensing of breast milk derived epidermal growth factor (EGF) and the blooming gut microbiota. Disruption of GAP formation and antigen delivery during this time in early life abrogated tolerance to dietary antigens, decreased regulatory T cells, and induced a skewing of the immune system toward systemic Th2 responses. We propose that maternal control of antigen delivery during infancy allows for the proper education of the immune system against dietary and microbial antigens, and induction of regulatory T cells necessary to suppress inappropriate Th2 responses later in life.