Akila Rekima1, Chrystelle Bonnart2, Patricia Macchiaverni1, Jessica Metcalfe3, Meri K Tulic4, Nicolas Halloin5, Samah Rekima6, Jon Genuneit7, Samantha Zanelli5, Samara Medeiros8, Debra J Palmer9, Susan Prescott10, Valerie Verhasselt11. 1. School of Molecular Sciences, University of Western Australia, Perth, Australia. 2. Institut National de la Santé et de la Recherche Médicale, U1220, Toulouse, France. 3. Telethon Kids Institute, University of Western Australia, Perth, Australia. 4. EA6302 Immune Tolerance, Université de Nice Sophia-Antipolis, Nice, France; Institut National de la Santé et de la Recherche Médicale, U1065, Mediterranean Centre for Molecular Medicine, Team 12, Nice, France; inVIVO Global Network, Research Group of the Worldwide Universities Network, West New York, NJ. 5. EA6302 Immune Tolerance, Université de Nice Sophia-Antipolis, Nice, France. 6. Institut Biologie Valrose, Université Côte d'Azur, Institut National de la Santé et de la Recherche Medicale, Centre National de la Recherche Scientifique, Nice, France. 7. inVIVO Global Network, Research Group of the Worldwide Universities Network, West New York, NJ; Pediatric Epidemiology, Department of Pediatrics, University of Leipzig Medical Center, Leipzig, Germany. 8. EA6302 Immune Tolerance, Université de Nice Sophia-Antipolis, Nice, France; Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 9. Telethon Kids Institute, University of Western Australia, Perth, Australia; inVIVO Global Network, Research Group of the Worldwide Universities Network, West New York, NJ. 10. Telethon Kids Institute, University of Western Australia, Perth, Australia; inVIVO Global Network, Research Group of the Worldwide Universities Network, West New York, NJ; Perth Childrens Hospital, Perth, Australia; School of Medicine, University of Western Australia, Crawley, Australia. 11. School of Molecular Sciences, University of Western Australia, Perth, Australia; inVIVO Global Network, Research Group of the Worldwide Universities Network, West New York, NJ. Electronic address: valerie.verhasselt@uwa.edu.au.
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.
RCT Entities:
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.
Authors: Mohamed H Shamji; Rudolf Valenta; Theodore Jardetzky; Valerie Verhasselt; Stephen R Durham; Peter A Würtzen; R J Joost van Neerven Journal: Allergy Date: 2021-06-08 Impact factor: 14.710