@article{f35864f46b284906a184449bf6f1be78,
title = "A role for early oral exposure to house dust mite allergens through breast milk in IgE-mediated food allergy susceptibility",
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.",
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",
author = "Akila Rekima and Chrystelle Bonnart and Patricia Macchiaverni and Jessica Metcalfe and Tulic, {Meri K} and Nicolas Halloin and Samah Rekima and Jon Genuneit and Samantha Zanelli and Samara Medeiros and Palmer, {Debra J} and Susan Prescott and Valerie Verhasselt",
note = "Funding Information: This work was supported by Institut Th{\'e}matique Multi-Organismes Immunologie, h{\'e}matologie, pneumologie (IHP)- Circulation, metabolisme, nutrition (CMN) of the Institut National de la Sant{\'e} et Recherche M{\'e}dicale , by Universit{\'e} de Nice Sophia Antipolis , Fonds de Dotation “Recherche en Sant{\'e} Respiratoire ,” Soci{\'e}t{\'e} Fran{\c c}aise d'Allergologie , Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de N{\'i}vel Superior (CAPES)- Comit{\'e} fran{\c c}ais d'Evaluation de la Coop{\'e}ration universitaire et scientifique avec le Br{\'e}sil (COFECUB) program (no. 867/15), the Larsson-Rosenquist Foundation , and the University of Western Australia . Funding Information: This work was supported by Institut Th{\'e}matique Multi-Organismes Immunologie, h{\'e}matologie, pneumologie (IHP)-Circulation, metabolisme, nutrition (CMN) of the Institut National de la Sant{\'e} et Recherche M{\'e}dicale, by Universit{\'e} de Nice Sophia Antipolis, Fonds de Dotation “Recherche en Sant{\'e} Respiratoire,” Soci{\'e}t{\'e} Fran{\c c}aise d'Allergologie, Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de N{\'i}vel Superior (CAPES)-Comit{\'e} fran{\c c}ais d'Evaluation de la Coop{\'e}ration universitaire et scientifique avec le Br{\'e}sil (COFECUB) program (no. 867/15), the Larsson-Rosenquist Foundation, and the University of Western Australia. Publisher Copyright: {\textcopyright} 2020 American Academy of Allergy, Asthma & Immunology",
year = "2020",
month = may,
doi = "10.1016/j.jaci.2019.12.912",
language = "English",
volume = "145",
pages = "1416--1429.e11",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "5",
}