Toll-like receptor 2 impacts the development of oral tolerance in mouse pups via a milk-dependent mechanism

Allergen shedding in human milk: Could it be key for immune system education and allergy prevention?

“…Rodent experiments further demonstrate a causal relation between allergen exposure through breast milk and allergy risk in offspring. [38][39][40][41][42][43][44][45] Preliminary evidence in observational birth cohorts where allergens were measured in breast milk supports the concept of an impact of allergen in human milk on offspring's allergy risk. 24,25,36 However, the lack of consistency in birth cohorts on the relationship between maternal allergen intake during breast-feeding and allergic outcome in offspring 8,9,46 highlights 2 major gaps in knowledge: (1) what parameters control allergen shedding in human milk and (2) which allergen characteristics and/or milk properties are required for oral tolerance induction to allergen in human milk.…”

“…Exposing lactating mice to egg antigen ovalbumin (OVA) by oral or intranasal route has been demonstrated to result in antigen transfer into the milk, 38,39 and this proved to be an efficient way to induce oral tolerance in offspring. [38][39][40][41][42][43][44][45] OVA-exposed lactating mice that are lacking adaptive immunity were still able to induce oral tolerance in offspring, 38 strongly arguing that it is the presence of the antigen itself in breast milk that is leading to oral tolerance. The plasticity of immune responses induced in offspring by antigen shedding in breast milk was exemplified with HDM allergens (Fig 1).…”

“…Data from rodent experiments indicated that transfer of deaggregated human gamma-globulin, 56 BSA, 57 or OVA [38][39][40][41][42][43][44][45] induced oral tolerance in offspring on their transfer through breast milk of naive mothers (and even if mothers are devoid of adaptive immunity 38 ). In contrast, peanut and cow milk require prior maternal immunity to these allergens to elicit protection in offspring on their transfer through breast milk.…”

“…40 A recent study in mice further suggested the importance of milk-derived insulin-like growth factor (IGF)-1 for oral tolerance induction to OVA in breast milk. 45 The data on the role of TGF-b in human milk in allergy prevention are conflictual. 87 However, no study so far has addressed whether the risk of food allergy in children exposed to OVA through human milk varied with the accompanying levels of TGF-b.…”

Role of innate immunity and myeloid cells in susceptibility to allergic disease

“…82,83 Oral exposure to TLR2 plays an important role in the development of neonatal oral tolerance in mice through the generation of regulatory intestinal DCs and the generation of T reg cells. 84 Therefore, modulation of the surface expression of these receptors on DCs or epithelial cells may alter the likelihood of an allergic or tolerance response to allergens. Figure 3 summarizes key immune pathways related to exposures and protection from allergic disease.…”