TY - JOUR
T1 - A role for early oral exposure to house dust mite allergens through breast milk in IgE-mediated food allergy susceptibility
AU - Rekima, Akila
AU - Bonnart, Chrystelle
AU - Macchiaverni, Patricia
AU - Metcalfe, Jessica
AU - Tulic, Meri K
AU - Halloin, Nicolas
AU - Rekima, Samah
AU - Genuneit, Jon
AU - Zanelli, Samantha
AU - Medeiros, Samara
AU - Palmer, Debra J
AU - Prescott, Susan
AU - Verhasselt, Valerie
N1 - Funding Information:
This work was supported by Institut Thématique Multi-Organismes Immunologie, hématologie, pneumologie (IHP)- Circulation, metabolisme, nutrition (CMN) of the Institut National de la Santé et Recherche Médicale , by Université de Nice Sophia Antipolis , Fonds de Dotation “Recherche en Santé Respiratoire ,” Société Française d'Allergologie , Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)- Comité français d'Evaluation de la Coopération universitaire et scientifique avec le Brésil (COFECUB) program (no. 867/15), the Larsson-Rosenquist Foundation , and the University of Western Australia .
Funding Information:
This work was supported by Institut Thématique Multi-Organismes Immunologie, hématologie, pneumologie (IHP)-Circulation, metabolisme, nutrition (CMN) of the Institut National de la Santé et Recherche Médicale, by Université de Nice Sophia Antipolis, Fonds de Dotation “Recherche en Santé Respiratoire,” Société Française d'Allergologie, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-Comité français d'Evaluation de la Coopération universitaire et scientifique avec le Brésil (COFECUB) program (no. 867/15), the Larsson-Rosenquist Foundation, and the University of Western Australia.
Publisher Copyright:
© 2020 American Academy of Allergy, Asthma & Immunology
PY - 2020/5
Y1 - 2020/5
N2 - 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.
AB - 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.
KW - Administration, Oral
KW - Adult
KW - Allergens/administration & dosage
KW - Animals
KW - Antigens, Dermatophagoides/administration & dosage
KW - Arthropod Proteins/administration & dosage
KW - CD4-Positive T-Lymphocytes
KW - Cysteine Endopeptidases/administration & dosage
KW - Dermatophagoides pteronyssinus/immunology
KW - Disease Susceptibility
KW - Double-Blind Method
KW - Egg Hypersensitivity/immunology
KW - Female
KW - Humans
KW - Immunoglobulin E/immunology
KW - Infant, Newborn
KW - Interleukin-33
KW - Intestine, Small/immunology
KW - Male
KW - Mice, Inbred BALB C
KW - Mice, Transgenic
KW - Milk/immunology
KW - Ovalbumin/administration & dosage
KW - Pregnancy
KW - protease
KW - breast-feeding
KW - House dust mite
KW - food allergy
UR - http://www.scopus.com/inward/record.url?scp=85079428735&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2019.12.912
DO - 10.1016/j.jaci.2019.12.912
M3 - Article
C2 - 31954775
SN - 0091-6749
VL - 145
SP - 1416-1429.e11
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 5
ER -