Abstract
BACKGROUND: Successful prevention of food allergy requires the identification of the factors adversely affecting the capacity to develop oral tolerance to food antigen in early life.
OBJECTIVES: This study sought to determine whether oral exposure to Dermatophagoides pteronyssinus through breast milk affects gut mucosal immunity with long-term effects on IgE-mediated food allergy susceptibility.
METHODS: Gut immunity was explored in 2-week-old mice breast-fed by mothers exposed to D pteronyssinus, protease-inactivated D pteronyssinus, or to PBS during lactation. We further analyzed oral tolerance to a bystander food allergen, ovalbumin (OVA). In a proof-of-concept study, Der p 1 and OVA levels were determined in 100 human breast milk samples and the association with prevalence of IgE-mediated egg allergy at 1 year was assessed.
RESULTS: Increased permeability, IL-33 levels, type 2 innate lymphoid cell activation, and Th2 cell differentiation were found in gut mucosa of mice nursed by mothers exposed to D pteronyssinus compared with PBS. This pro-Th2 gut mucosal environment inhibited the induction of antigen-specific FoxP3 regulatory T cells and the prevention of food allergy by OVA exposure through breast milk. In contrast, protease-inactivated D pteronyssinus had no effect on offspring gut mucosal immunity. Based on the presence of Der p 1 and/or OVA in human breast milk, we identified groups of lactating mothers, which mirror the ones found in mice to be responsible for different egg allergy risk.
CONCLUSIONS: This study highlights an unpredicted potential risk factor for the development of food allergy, that is, D pteronyssinus allergens in breast milk, which disrupt gut immune homeostasis and prevents oral tolerance induction to bystander food antigen through their protease activity.
Original language | English |
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Pages (from-to) | 1416-1429.e11 |
Journal | Journal of Allergy and Clinical Immunology |
Volume | 145 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2020 |
Externally published | Yes |
Keywords
- Administration, Oral
- Adult
- Allergens/administration & dosage
- Animals
- Antigens, Dermatophagoides/administration & dosage
- Arthropod Proteins/administration & dosage
- CD4-Positive T-Lymphocytes
- Cysteine Endopeptidases/administration & dosage
- Dermatophagoides pteronyssinus/immunology
- Disease Susceptibility
- Double-Blind Method
- Egg Hypersensitivity/immunology
- Female
- Humans
- Immunoglobulin E/immunology
- Infant, Newborn
- Interleukin-33
- Intestine, Small/immunology
- Male
- Mice, Inbred BALB C
- Mice, Transgenic
- Milk/immunology
- Ovalbumin/administration & dosage
- Pregnancy
- protease
- breast-feeding
- House dust mite
- food allergy