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1. Ovalbumin in breastmilk is associated with a decreased risk of IgE‐mediated egg allergy in children

Author

Meri K. Tulic, Akila Rekima, Debra J. Palmer, Susan L Prescott, Jessica Metcalfe, Valérie Verhasselt, and Jon Genuneit

Subjects
Milk, Human, Allergy prevention, biology, Ovalbumin, business.industry, Immunology, Breastfeeding, Infant, Allergens, Immunoglobulin E, medicine.disease, Ige mediated, Egg allergy, Primary prevention, medicine, biology.protein, Animals, Humans, Immunology and Allergy, Child, Egg Hypersensitivity, business
Published
2020
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2. Allergen shedding in human milk: Could it be key for immune system education and allergy prevention?

Author

Lieke W J van den Elsen, Valérie Verhasselt, Harald Renz, Akila Rekima, and Patricia Macchiaverni

Subjects
Risk, Allergy, Immunology, Breast milk, Gut flora, medicine.disease_cause, Allergen, Immune system, Immunity, medicine, Hypersensitivity, Immune Tolerance, Immunology and Allergy, Animals, Humans, biology, Milk, Human, business.industry, food and beverages, Extracellular vesicle, Allergens, biology.organism_classification, medicine.disease, Infectious disease (medical specialty), Immune System, Female, business
Abstract

In addition to being a source of nutrients for the developing newborn, human milk contains thousands of bioactive compounds, which influence infant health in the short-term as exemplified by its major benefits on infectious disease prevention. Many of the human milk compounds also have the required characteristics to instruct immune development and guide long-term health. Prebiotics, probiotics, and varied antimicrobial molecules all have the potential to shape the composition and function of the establishing gut microbiota, which is known to be a major determinant of immune function. Another and less explored way human milk can instruct long-term immunity is through antigen shedding. Here, we will review the evidence that antigens from maternal environment and more specifically from allergen sources are found in human milk. We will discuss data from rodent models and birth cohorts showing that allergen shedding in breast milk may influence long-term allergy risk. We will uncover the variables that may underlie heterogeneity in oral tolerance induction and allergy prevention in children breast-fed by allergen-exposed mothers. We will focus on the parameters that control antigen transfer to breast milk, on the unique biological characteristics of allergens in breast milk, and on the milk bioactive compounds that were found to influence immune response in offspring. We propose this understanding is fundamental to guide maternal interventions leading to lifelong allergen tolerance.

Published
2021

3. The presence of both hen’s egg Ovalbumin allergen and Ovalbumin specific Immunoglobulin in breastmilk is associated with decreased risk of egg allergy in infants

Author

J. Metcalfe, Akila Rekima, Valérie Verhasselt, Meri K. Tulic, Susan L. Prescott, Jon Genuneit, and Debbie Palmer

Subjects
Pulmonary and Respiratory Medicine, lcsh:Immunologic diseases. Allergy, biology, business.industry, Immunology, medicine.disease, medicine.disease_cause, Ovalbumin, Allergen, Egg allergy, biology.protein, Immunology and Allergy, Medicine, Antibody, business, lcsh:RC581-607
Published
2020

4. Saccharomyces boulardii Strain CNCM I-745 Modifies the Mononuclear Phagocytes Response in the Small Intestine of Mice Following Salmonella Typhimurium Infection

Author

Lidia Ibáñez, Rodolphe Pontier-Bres, Frederic Larbret, Akila Rekima, Valérie Verhasselt, Claudine Blin-Wakkach, Dorota Czerucka, UCH. Departamento de Farmacia, and Producción Científica UCH 2019

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, Saccharomyces boulardii - Therapeutical use, bone marrow, Intestinos - Inmunología, Phagocytosis, Immunology, Inflammation, Salmonella Typhimurium - Treatment, Biology, Salmonella Typhimurium - Tratamiento, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Enfermedades infecciosas - Inmunoterapia, medicine, Saccharomyces boulardii - Uso terapéutico, Immunology and Allergy, Mesenteric lymph nodes, innate immunity, Saccharomyces boulardii CNCM I-745, Original Research, Lamina propria, Innate immune system, Probióticos, Monocyte, Intestines - Immunology, Probiotics, biology.organism_classification, Communicable diseases - Immunotherapy, infection, 030104 developmental biology, medicine.anatomical_structure, Salmonella Typhimurium, medicine.symptom, monocytes, lcsh:RC581-607, probiotic, 030215 immunology, Saccharomyces boulardii
Abstract

Este artículo se encuentra disponible en la siguiente URL: https://www.frontiersin.org/articles/10.3389/fimmu.2019.00643/full Intestinal mononuclear phagocytes (MPs) comprise dendritic cells (DCs) and macrophages (M0s) that play different roles in response to Salmonella infection. After phagocytosis, DCs expressing CD103 transport Salmonella from the intestinal tract to the mesenteric lymph nodes (MLN) and induce adaptive immune responses whereas resident M0s expressing CX3CR1 capture bacteria in the lumen and reside in the lamina propria (LP) where they induce a local immune response. CX3CR1+ M0s are generated from Ly6Chi monocytes that enter the colonic mucosa and differentiate locally. We previously demonstrated that the probiotic yeast Saccharomyces boulardii CNCM I-745 (S.b) prevents infection by Salmonella enterica serovar Typhimurium (ST), decreases ST translocation to the peripheral organs and modifies the pro-and anti-inflammatory cytokine profiles in the gut. In the present study, we investigated the effect of S.b on the migratory CD103+ DCs and the resident CX3CR1+ M0s. MPs were isolated from the LP of streptomycin-treated mice infected by ST with or without S.b treatment before or during the infection. In S.b-pretreated mice, we observed a decrease of the CD103+ DCs in the LP that was associated with the drop of ST recovery from MLN. Interestingly, S.b induced an infiltration of LP by classical Ly6Chi monocytes, and S.b modified the monocyte-M0 maturation process in ST-infected mice. Our results showed that S.b treatment induced the expansion of Ly6Chi monocytes in the blood as well as in the bone marrow (BM) of mice, thus contributing to the M0 replenishment in LP from blood monocytes. In vitro experiments conducted on BM cells confirmed that S.b induced the expansion of CX3CR1+ M0s and concomitantly ST phagocytosis. Altogether, these data demonstrate that Saccharomyces boulardii CNCM I-745 modulates the innate immune response. Although here, we cannot explicitly delineate direct effects on ST from innate immunity, S. b-amplified innate immunity correlated with partial protection from ST infection. This study shows that S.b can induce the expansion of classical monocytes that are precursors of resident M0s in the LP.

Published
2019
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5. Long-term reduction in food allergy susceptibility in mice by combining breastfeeding-induced tolerance and TGF-β-enriched formula after weaning

Author

Valérie Verhasselt, Sébastien Holvoet, Patricia Macchiaverni, Annick Mercenier, Akila Rekima, Sophie Nutten, M. Turfkruyer, Lénaïck Dupuis, Nour Baïz, and Isabella Annesi-Maesano

Subjects
Diarrhea, 0301 basic medicine, Ovalbumin, Immunology, Breastfeeding, Weaning, Breast milk, Immunoglobulin E, Mice, 03 medical and health sciences, Antibody Specificity, T-Lymphocyte Subsets, Transforming Growth Factor beta, Food allergy, Lactation, Immune Tolerance, Animals, Humans, Immunology and Allergy, Medicine, Intestinal Mucosa, Milk, Human, biology, business.industry, medicine.disease, Animal Feed, Breast Feeding, 030104 developmental biology, medicine.anatomical_structure, Immunoglobulin G, biology.protein, medicine.symptom, business, Food Hypersensitivity
Abstract

Background Oral tolerance induction in early life is a promising approach for food allergy prevention. Its success requires the identification of factors necessary for its persistence. Objectives We aimed to assess in mice duration of allergy prevention by breastfeeding-induced oral tolerance and whether oral TGF-β supplementation after weaning would prolong it. Methods We quantified ovalbumin (OVA) and OVA specific immunoglobulins levels by ELISA in milk from the EDEN birth cohort. Since OVA specific Ig were found in all samples, we assessed whether OVA-immunized mice exposed to OVA during lactation could prevent allergic diarrhea in their 6 and 13-week-old progeny. In some experiments, a TGF-β enriched formula was given after weaning. Results At 6 weeks, only 13% and 34% of mice breastfed by OVA-exposed mothers exhibited diarrhea after 6 and 7 OVA challenges versus 44% and 72% in mice breastfed by naive mothers (p=0.02 and 0.01). Protection was associated with decreased levels of MMCP1 and OVA specific IgE (p

Published
2017
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6. A role for early oral exposure to house dust mite allergens through breast milk in IgE-mediated food allergy susceptibility

Author

Samara Rabelo Medeiros, Debra J. Palmer, Jessica Metcalfe, Samantha Zanelli, Nicolas Halloin, Susan L. Prescott, Patricia Macchiaverni, Valérie Verhasselt, Chrystelle Bonnart, Meri K. Tulic, Jon Genuneit, Akila Rekima, Samah Rekima, School of Molecular Sciences, The University of Western Australia (UWA), Institut National de la Santé et de la Recherche Médicale (INSERM), Telethon KIDS Institute, Université de Nice Sophia-Antipolis (UNSA), Worldwide Universities Network, Partenaires INRAE, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire LTEE, Universidade Federal de Minas Gerais, University of Western Australia, ProdInra, Migration, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)

Subjects
CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Dermatophagoides pteronyssinus, Administration, Oral, 0302 clinical medicine, Pregnancy, Lactation, Intestine, Small, Immunology and Allergy, 2. Zero hunger, Mice, Inbred BALB C, biology, Innate lymphoid cell, 3. Good health, Cysteine Endopeptidases, Milk, medicine.anatomical_structure, Female, Disease Susceptibility, Adult, Ovalbumin, Immunology, Mice, Transgenic, Breast milk, Arthropod Proteins, House dust mite, 03 medical and health sciences, Double-Blind Method, Food allergy, medicine, Animals, Humans, Antigens, Dermatophagoides, Egg Hypersensitivity, food allergy, business.industry, Infant, Newborn, protease, Allergens, Immunoglobulin E, Interleukin-33, biology.organism_classification, medicine.disease, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, 030228 respiratory system, breast-feeding, Egg allergy, biology.protein, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Breast feeding
Abstract

International audience; 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. © 2020 American Academy of Allergy, Asthma & Immunology

Published
2020
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7. Early-Life Nutrition and Gut Immune Development

Author

Lieke W J van den Elsen, Valérie Verhasselt, and Akila Rekima

Subjects
Allergy, biology, animal diseases, chemical and pharmacologic phenomena, Disease, biochemical phenomena, metabolism, and nutrition, medicine.disease, Aryl hydrocarbon receptor, Inflammatory bowel disease, Early life, Immune system, Immunology, medicine, biology.protein, bacteria, Mucosal immunity, Function (biology)
Abstract

Gut immune function conditions the development of local and systemic diseases that result from defects in immune regulation, such as inflammatory bowel disease, allergy and obesity. As epidemiological studies support the developmental origin of health and disease, deciphering the critical factors modulating gut immune development should allow the advance of primary prevention strategies specifically adapted to the early-life immune system. Here, we will review gut mucosal immunity development and cover in more detail the recent understanding of the impact of early nutrition on this process. We will emphasize how nutrition can shape microbiota composition and metabolic function and thereby the production of metabolites with immune-modulatory properties. We will also focus on the role of dietary compounds recently demonstrated to be essential in immune development and function, such as dietary antigens, vitamin A, and aryl hydrocarbon receptor ligands. Finally, we will discuss that early-life physiologic food for mammals contains factors capable of compensating for neonatal immune deficiencies, but also factors that are decisive for immune maturation towards a maternal milk-independent and efficient immune system.

Published
2019
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8. Presence of commensal house dust mite allergen in human gastrointestinal tract: a potential contributor to intestinal barrier dysfunction

Author

Akila Rekima, Thierry Piche, Mylene Vivinus-Nébot, Julien Boyer, Meri K. Tulic, Nathalie Vergnolle, Valérie Verhasselt, Chrystelle Bonnart, Raffaella Dainese, Allan Walker, Haining Shi, and Samara Rabelo Medeiros

Subjects
0301 basic medicine, Gastrointestinal Diseases, Dermatophagoides pteronyssinus, medicine.medical_treatment, Inflammation, medicine.disease_cause, digestive system, Mice, 03 medical and health sciences, Allergen, medicine, Animals, Humans, Antigens, Dermatophagoides, House dust mite, Mice, Inbred BALB C, Gastrointestinal tract, biology, digestive, oral, and skin physiology, Human gastrointestinal tract, Mucin, Gastroenterology, biology.organism_classification, Gastrointestinal Tract, 030104 developmental biology, medicine.anatomical_structure, Cytokine, Immunology, Tumor necrosis factor alpha, medicine.symptom
Abstract

Abnormal gut barrier function is the basis of gut inflammatory disease. It is known that house dust mite (HDM) aero-allergens induce inflammation in respiratory mucosa. We have recently reported allergen from Dermatophagoides pteronyssinus (Der p1) to be present in rodent gut.To examine whether Der p1 is present in human gut and to assess its effect on gut barrier function and inflammation.Colonic biopsies, gut fluid, serum and stool were collected from healthy adults during endoscopy. Der p1 was measured by ELISA. Effect of HDM was assessed on gut permeability, tight-junction and mucin expression, and cytokine production, in presence or absence of cysteine protease inhibitors or serine protease inhibitors. In vivo effect of HDM was examined in mice given oral HDM or protease-neutralised HDM. Role of HDM in low-grade inflammation was studied in patients with IBS.HDM Der p1 was detected in the human gut. In colonic biopsies from healthy patients, HDM increased epithelial permeability (p0.001), reduced expression of tight-junction proteins and mucus barrier. These effects were associated with increased tumour necrosis factor (TNF)-α and interleukin (IL)-10 production and were abolished by cysteine-protease inhibitor (p0.01). HDM effects did not require Th2 immunity. Results were confirmed in vivo in mice. In patients with IBS, HDM further deteriorated gut barrier function, induced TNF-α but failed to induce IL-10 secretion (p0.001).HDM, a ubiquitous environmental factor, is present in the human gut where it directly affects gut function through its proteolytic activity. HDM may be an important trigger of gut dysfunction and warrants further investigation.

Published
2015
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9. Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

Author

Georgios Rentzos, Esben Eller, Annick Mercenier, Magna Correia, Pedro Moreira, Linda Verrill, Mário Morais-Almeida, Frauke Schocker, Carsten Bindslev-Jensen, Ulrike Lehnigk, Andreas Frey, Lars Verschuren, Anna-Lena Bramstång Björk, Lene Heise Garvey, Elena Molina, Katrine L. Bøgh, J. L. van der Velde, Montserrat Alvaro, Phil Padfield, Niamh Brosnan, Nelly Gourdon-Dubois, Christian Harwanegg, Manuel Branco Ferreira, Songül Yürek, Amyra Ali Azamar Jácome, Rashid Amin, José Ramón Fernández Lorenzo, Kirsten Beyer, Florin-Adrian Secureanu, Charlotte Bernhard Madsen, Julie Galand, Claudia Pföhler, Rabea Reinert, Heinz Fehrenbach, Anton Hartmann, Maria Salas, Arne Homann, Rand Arnaout, Sarah Lindsley, Nerea Sarmiento Carrera, Patrícia Padrão, Berber Vlieg-Boerstra, Alkerta Ibranji, Benoît Sterling, Maria Auxiliadora Guerrero, Maria L. Baeza, Maurizio Tamburrini, Eva Untersmayr, Tanja Cirkovic Velickovic, Farrukh Sheikh, Sarah Kuntz, Sara Martínez, Kriti Gupta, Maria de Lurdes Torre, Yvonne Vergouwe, Ross Yarham, Faisal R. Bakhsh, Marta Vazquez-Ortiz, João Marcelino, Tullio Frediani, Ricardo Prata, Anna Kaarina Kukkonen, Gustavo Soldateli, Ines Mrakovčić-Šutić, Elodie Drumez, Cristina Ornelas, Maria Vazquez de La Torre, Renata Barros, Agata Szymkiewicz, Aneta Tomaszewska, Stefanie Rohwer, Charlotte Eisenmann, Adriana Muntean, Matteo Moretti, Johanna P. M. van der Valk, Birgit Quinting, Stefan Kabasser, David Gillick, Michał Przybyszewski, Grzegorz Sergiejko, Antonio Jorge Cabral, Alba Pablos-Tanarro, Robert Elfont, Marit Reitsma, Roxana Silvia Bumbăcea, Nelson Rosario, Maria Livia Bernardi, Cristiane N. Santos, Christian Radauer, Sandra Denery-Papini, Geert F. Houben, Nicolette W. de Jong, Marta Anda, Alexander Rohrbach, Teodorikez Wilfox Jimenez-Rodriguez, María Teresa Villalba, Karine Patient, Harmieke van Os-Medendorp, Kathrin Scherer, Marta Goñi Esarte, Svetlan Dermendzhiev, Jossie Garthoff, Michelle M. Epstein, Catherine Bertholet, Bruna Pultrini Aquilante, Didier G. Ebo, Roberta Aina, Jorge Kalil, Petri Kulmala, Lars K. Poulsen, Barbara Ballmer, H. Mary-Lene de Zeeuw-Brouwer, Karin Hoffman-Sommergruber, Winfried Leeman, Anne Miles, Nehad Gomaa, Maria Teresa Costantino, Evelyne Mangodt, Maria Konstantakopoulou, Rosa Jimenez, Attilio Francesco Speciani, Helga Magnusdottir, Inmaculada Sánchez-Machín, H. Kaddouri, Raquel Perez, Astrid Versluis, Anthony E. J. Dubois, Anja Koren Jeverica, Zdenka Barićev-Novaković, Joost Westerhout, A.M. Plaza, Júlio Oliveira, Pierre Lukas, Oksana Matsyura, Giuseppe Pingitore, Mira Silar, Huub F. J. Savelkoul, Urszula Samolinska-Zawisza, Chantal Brossard, Ana Reis Ferreira, Reiko Teshima, Serena Perna, Mariola Dietrich, Dirk Verhoeven, Fiona Kenna, Paloma Poza-Guedes, Cristobalina Mayorga, Pilar Hernandez, Roberto Bernardini, Roberto Berni Canani, Maria Francesca Patria, Mariana Vieru, Julie Locklear, Esther van Twuijver, Marina A. Kiseleva, H. Kim A. Brand, Gabriele Schulz, Ileana-Maria Ghiordanescu, Nikolaos G. Papadopoulos, Danijela Apostolovic, Maria del Mar Folqué, Eva Lasa, Mohammad Al Bahkali, Arianna Dondi, Sofia Kostoudi, Simon Rosenberg, Véronique Nève, Rumyana Yankova, Barbara Ballmer-Weber, Maria Jose Goikoetxea, María José Barasona Villarejo, Teija Dunder, Tina Vesel, Elisa Gritti, Marianne van Hage, Laure Castan, Etienne Beaudouin, Margherita Di Costanzo, Natalia Ukleja-Sokołowska, Matthew Sperrin, Paul Turner, Saskia Albroscheit, Rebeca Lopez, Sonja Posega Devetak, Francisca Palomares, Laetitia Sellam, Jennifer Hammond, Astrid G. Kruizinga, Konrad Furmanczyk, Patricia Macchiaverni, Olga Pakholchuk, I V Vorozhko, Ania Carsin, Aleksandar Bulog, Joris Mens, Bianca Balbino, James P. Hindley, Jaap H. Akkerdaas, Jonathan Hourihane, Hilde Cnossen, Tatyana A Popova, Rupert Schlags, Natalia Nenasheva, A. Ehrenberg, Sigurveig T. Sigurdardottir, Anna Iliopoulou, Clara Ippolito, Piotr Samel-Kowalik, Paloma Campo, Gador Bogas, Constantinos Pitsios, Sarah Grosche, Karla Leversia Borjas Aguilar, Amena Warner, Birgit Kalb, Lénaïck Dupuis, Harry J. Wichers, Diana Silva, Gabriele Piuri, Linus Grabenhenrich, Emanuel Sarinho, M. Eleonore Pettersson, Rodrigo Barderas, Gary Stiefel, E. N. Clare Mills, Lali Saginadze, Ruta Dubakiene, Francesca Cipriani, Mindy Tsai, Marina Themisb, Michela Ciancamerla, Rebecca Knibb, Ruperto González-Pérez, Marina Peredelskaya, André C. Knulst, Irene Berends, S N Denisova, Montserrat Fernandez-Rivas, Paolo Maria Matricardi, Daniel Sampaio, Giorgio Bedogni, Sira Miquel, Koen Smit, Stefania Arasi, Sylvia Osscini, Justine Courtois, Cristina Deaconu, Srdan Banac, Kirsten Hansen, Jennette Higgs, Charlotte Hands Plovdiv, Carlotta Povesi Dascola, Noe Ontiveros, Rik Schrijvers, Carla Mastrorilli, Maria Passioti, Sebastian Tschirner, Bjorn R. Ludviksson, Joana Caiado, Daniel Corbacho, Sophie Nutten, Agustin Madroñero, Marina Suárez Vergara, Boudewjin J. Kollen, Catherine J Nock, Johanna Rost, Agnieszka Lipiec, Skadi Kull, Geert Houben, Carlo Caffarelli, Jordi Roca-Ferrer, Bolesław Samoliński, Isabelle Cleach, Colette Larré, Aideen Byrne, Corinne Herouet-Guicheney, Jonas Lidholm, Vera Assmann, W. Marty Blom, Adriano Mari, Adam T. Fox, Giuseppe Crisafulli, Afke M. M. Schins, Anastasia Papadopoulou, Flávio Sano, Richard Cooke, Franziska Ruëff, L Jorjoliani, Rebekah Sayers, Anne-Marie Kochuyt, Borja Bartalomé, Anne Moneret-Vautrin, Juan Carlos Julia, Jelena Mihailovic, Katarzyna Pyrz, Kollen Boudewijn, Margherita Varini, Paolo Giordani, Claudia Alessandri, Johanna van der Valk, Antoine Deschildre, Mariam Tskhakaia, Rosina López-Fandiño, Omar Kheroua, Nicolette J. T. Arends, Alina Zbróg, Chung-Hsiung Huang, Andrea Wangorsch, Ulf Bengtsson, Jim Langridge, Dasha Roa-Medellín, Jose Ignacio Larco, Bert Popping, Ana Prieto del Prado, José Antonio Bácter Martos, Rita Nocerino, Sophia Watts, Elisa Haroun, Danilo Villalta, Lee A. Gethings, María Ángeles Algaba Mármol, Ewa Gawrońska-Ukleja, Cornelia Jansen, André Moreira, V A Revyakina, Robert Zacniewski, Xavier Domingo Miró, Francesco Macrì, Mayra de Barros Dorna, Akanksha Sharma, Stephen J. Till, Ali Almontasheri, Chrystyna Kalicinsky, Robbert Sutorius, Akila Rekima, Mark A. Blankestijn, Nicolette Arends, Chiara Pistoletti, Merima Bublin, Manuel Pereira-Barbosa, Reyna Simon, Martin Karjalainen, Sam Mehr, Tushar Banerjee, Carmen Riggioni, Bertrand Evrard, Antonio Carlos Pastorino, Lidia Ilènko, Nikolaos Douladiris, Miguel Vieira, Erik Wambre, Francisco Cabrera-Chavez, Nikos G. Papadopoulos, Piotr Humeniuk, Gert van Duijn, Francesco Zinno, Young-Ae Lee, Lisa Tuppo, Hans de Groot, Léon M.J. Knippels, Pawel Dubiela, Henrik Fomsgaard Kjaer, Andrea Vereda, Djamel Saidi, Kok Loong Ue, Henk Van Loveren, Maria Jose Rodriguez, Marta Lomikovska, Elodie Michaud, Josefina Cernadas, Carmen Ponce, Marysia Recto, Frances Smith, Hassan Al-Dhekri, Shinobu Sakai, Thomas Eiwegger, Ana Rodolfo, Diego Peroni, Nikki Edelbroek, Waltraud Suer, Jenny van Odijk, Irena Nedelea, Borja Bartolomé, Lauren Lissner, Marjeta Sedmak, Annette Jamin, Italo De Vitis, Bo Pontoppidan, Annabelle Capt, Diego G. Peroni, Susana Rodrigues, Juan Carlos López-Rodríguez, David Endesfelder, Lesya Besh, Danila Zennaro, Charlotte G. Mortz, Kati Palosuo, María José Torres, Esozia Arroabarren, Lynne Regent, Laura Valdesoiro Navarrete, Ana Molina, Agha Rehan Khaliq, Phil Couch, Ana Miranda, Thomas Marichal, Riccardo Asero, Denise Borges, Dikla Pivko Levy, Miriam Palacios, Mireille Eb, Stephen J. Galli, Karin Hoffmann-Sommergruber, Anna Gudrun Vidarsdottir, Ifigenia Sfika, André Wolterbeek, Mauro Calvani, Edward F. Knol, Joyce A. M. Emons, Anne-Marie Oomkes-Pilon, Montserrat Bosque García, Daniel Lozano-Ojalvo, Filip Raciborski, Deirdre Galloway, Nanna Juel-Berg, Margareta Brandt Gertmo, Cornelia Bergmayr, Rob Klemans, Juliane Gregersen, Yolanda Meijer, Bettina Brix, Susanne Lau, Karine Adel-Patient, Hanneke van der Kleij, Mareike Price, Jean-Louis Mege, Lizalet Oosthuizen, Agurtzane Bilbao, Indre Butiene, Antonino Romano, Colin Barber, Rosana Camara Agondi, Nour Baïz, Soraya Ainad Tabet, Peter Korošec, Laurian Jongejan, Francine C. van Erp, José Pedro Moreira Silva, Nandinee Patel, Jaime Lozano, Prescilla V. Jeurink, Artur Walkiewicz, Bryan M. Harvey, Tiina J. Kauppila, Aida Semic-Jusufagic, Marianna Murdjeva, Miren Arteaga, Y. Bouferkas, Geunwoong Noh, Henny G. Otten, Sabine Dölle, Christopher Munro, O Dominguez, Gerard H. Koppelman, Leonieke N. van Veen, Vasti Iancu, Georg Mitterer, Patrizia Polverino de Laureto, Juliane Schulz, Ewa Ternesten Hasseus, Caroline Zimmermann, Ivona Barcievic-Jones, Shira Benor, Susanne Schwarz, Eun Ha Jang, Josefina Rodrigues Cernadas, Tadej Avcin, Joseph L. Baumert, Pernille Winther, Stéphane Leteurtre, Gabriela Canto, Louise J Michaelis, Jorge Alvarez, Gabriel Gastaminza, Michela Carola Speciani, Rute Gonçalves, Leire Dopazo, Evgen Benedik, Susanne C. Diesner, Luc S. De Clerck, A. Wesley Burks, Maurits S. van Maaren, Salvatore Tripodi, Philippe Aubert, Kamel Eddine El Mecherfi, Aline B. Sprikkelman, Ana Prieto, Margitta Worm, Edyta Krzych, Maja Krstic, Iride Dello Iacono, Melanie Cap, Alf Weimann, Maria Nassiri, Niels Röckendorf, Vladyslava Barzylovych, Marcia C. Mallozi, Pierre Bruhns, Jeanette Fisker Trandbohus, Ekaterini Papadopoulou, Vicente Albendiz, Timothy Watts, Uta Jappe, Javier Moreno, Maria Carmen Verga, Beatriz Secades Barbado, Carmen Di Scala, Roy Gerth van Wijk, Vladimir Mićović, Esther Barrionuevo, Giampaolo Ricci, Luisa Galindo, Ana Paula Beltran Moschione Castro, Oona Mustonen, Jia Yin, Lucia Caminiti, Jorge Esparza-Gordillo, N Adamia, Anna-Maija Hanni, Romy Gadisseur, Stefano Luccioli, Regina Treudler, Rosetta Ferrara, M. Guendouz, Jaakko Yrjänä, Philipp Starkl, Premendra D. Dwivedi, Javier Cuesta-Herranz, Johan Garssen, Ekaterini Goudouris, Sridevi Muralidharan, Kate Grimshaw, Carolina Sanchez Aranda, Ioana Maris, Manzoor Ahmed, Hajime Karasuyama, Stephanie Claus, Chantal Agabriel, Karen English, Dorien Van Ginkle, Eleonora Savi, Loredana Chini, Ine I. Decuyper, Sabine Schnadt, Valérie Trendelenburg, Jean-Luc Fauquert, Maurizio Mennini, Nikolaos Mikos, Ana Célia Costa, Steve L. Taylor, A. A. Schoemaker, Sara Abián, Margo M. Hagendorens, Andrea Di Rienzo Businco, Melina Makatsori, Eugénia Matos, Lucy Walker, Nikolaos A. Kitsioulis, David Alejandro Mendoza Hernández, Maria Starkhammar, Djordje Filipovic, Aine Adams, Mukul Das, Sonsoles Intente-Herrero, Natalia Blanca López, Marek L. Kowalski, Diana Deleanu, Bernard P. Mahon, Jean-Michel Wal, Lucia Decastelli, Mihaela Popescu, Aimee Lou Nano, Eva Batanero, Tong-Rong Jan, Yolanda Puente, Jacek Borowicz, Aimée Dorkenoo, J. Östling, Mashary Altamimi, Michel Neunlist, Zerrin Yalvaç, Sonia Ricò, Wentong Xue, Linda Cosenza, David C. A. Candy, Robert D. Voyksner, Montserrat De Prada, Abdulhadi Al-Qahtani, Sébastien Holvoet, Wolf-Meinhard Becker, Meropi D. Kontogianni, Bruno Pereira, F. Pineau, Eva Corbet, Kirsten Mehlig, Rosella De Poi, Jolanda H. M. van Bilsen, José Luís Plácido, Hans-Jørgen Malling, Chia-Chi Wang, Philip Couch, Kerrie Kirk, Agata Michalska, Sylke Rietz, Mariya Ivanovska, Victor Matheu-Delgado, Carl Hamsten, Francisca Gómez, Neusa Falbo Wandalsen, Mika J. Mäkelä, Tatyana Sentsova, Kristian Bravin, Philippe Delahaut, Hervé Bernard, Leonor Carneiro-Leão, Michele Miraglia del Giudice, Elena D. Kuvshinova, Jochen Behrends, Caroline Klingebiel, Meta Accetto, Claire Mills, Mariona Pascal, Miguel García Domínguez, Huan Rao, Carmen Saviana Ganea, Umberto Pelosi, Stefano Pattini, Bodo Niggemann, Annamaria Bianchi, Laura Martín-Pedraza, Anna Selby, Cristina Bueno, Stefan Vieths, Luis Felipe Ensina, Florin-Dan Popescu, Antonio Fernandez, Soren Wille, Erna Van Hoeyveld, Carina Kelleher, Athina L. Van Gasse, Anders Blom Jensen, Zorica Zivkovic, Moshe Ben-Shoshan, Sara Pereiro Fernández, Ronald van Ree, Antima Banerjee, Pablo Merida, Mandy Ziegert, Barbara Wróblewska, Morten Christensen, Gador Gomez, Pablo San Segundo-Acosta, Khaled Messaoudi, Anne-Sofie Ravn Ballegaard, Mikael Kuitunen, David Luyt, Vito Sabato, Nesrine Zaabat, Svitlana Zubchenko, Julien Labreuche, Elin Lustig, Katharina Blumchen, Guillaume Pouessel, Ana Fiandor, Stéphanie Lejeune, Paola Dignetti, Helen Brown, Anastasia Cirisano, Evangelia Kompoti, Anna Sokolova, Mercedes Escarrer Jaume, Shan Deng, Dirceu Solé, Chiara Fiamingo, Alessandro Travaglini, Nicolas Gaudenzio, Zbigniew Bartuzi, Antonia Rojas, Roberta Olcese, Nanju Alice Lee, Sandra Brandhoff, Lucien F. Harthoorn, Anna Maria Szyc, Andrea Costanzi, Sabine Pfeifer, Emiliano De Dominicis, Chiara Rafaiani, Yin-Hua Cheng, Elida Nikolla, Ignacio García Núñez, Diego Faggian, Lieve Coorevits, Ayelet Rimon, Erika Jensen-Jarolim, Jacqueline J.M. Castenmiller, Kristin Verbeke, Sean Bennett, Paraskevi Xepapadaki, Glauce Hiromi Yonamine, Anna Wawrzeńczyk, Rusudan Karseladze, Emmanouil Manousakis, Fiona Ward, Ivana Filipovic, Marie Bodinier, Viviana Moschese, Pedro Giavina Bianchi, Alice Coimbra, Alena Berger, Anton A. Shekhetov, Monica Maćków, Philippe Egenmann, Oscar Asensio, Lidia Hanna Markiewicz, Chun-Wei Tung, Zsolt Szépfalusi, Jan Knol, Frits Koning, Carolina S. Aranda, Annick Bastiaensen, Giovanni Battista Pajno, Leticia Pérez-Rodríguez, Ewout W. Steyerberg, Riccardo Sibilano, Valérie Verhasselt, Roberta Lupi, Lukasz Sokolowski, Adam Wawrzeńczyk, Dimitris I. Mitsias, Andreia Forno, Antoine Magnan, Christian Schwager, Ioanna Manolaraki, Alessandro Fiocchi, Tanja Rouhani Rankouhi, Carla Jones, Ana Pereira, Hannah M. Kansen, Michael Clausen, D. Bignardi, Assad M. Butt, Julie C. Locklear, Katrine Lindholm Bøgh, Valery Muhortnich, María Teresa Giner, Juan Miguel Garcia, Maria Luisa Somoza, Raditsa Sokolova, Maria Pasioti, Mirjana Zupancic, Joana Vitte, Duncan Brown, Arnaldo Porto, M. Turfkruyer, Lau Fabricius Larsen, Filipe Benito-Garcia, Mayra Coutinho Andrade, Meltem Ugras, Ingrid Sutic, Rand K. Arnaout, Etienne Cavalier, Marta Neto, Grégory Bouchaud, Elena Varin, Bushra Javed, Carla Camerotto, Monica Bronkowska, Cristiano Caruso, Luís Amaral, Jackeline F. Motta, Sahar Elshorbagi, Cornelis K. van der Ent, Alexandra Rodrigues, Silvia Peveri, Juan Heber Castellanos, Muriel Totis, Joan Bartra, Gjustina Loloci, Ivana Giangrieco, Ekaterina Khaleva, Joaquín Navarro, Kayoko Matsunaga, Jlenia Fresta, Jonathan O'b Hourihane, Sabina Bijlsma, Ana Rodriguez-Fernandez, Rosita Aitoro, Daniela Manila Bianchi, Rosa Jimenez-Feijoo, Mario Plebani, Marleen T. J. Van Ampting, Anthony E.J. Dubois, Clémence Mordacq, Simone Frediani, Martin Chapman, Helena Larramona, Fabrícia Carolino, Yanne Boloh, Ivona Baricevic-Jones, Mathilde Claude, Caroline Thumerelle, Päivi Vähäsarja, Mareen R. Datema, Abdullah Alfhaid, Diana Perez Alzate, Laura Santos-Diez, Graham King, Maria Teresa Guerra Perez, Jean-Marie Renaudin, Frieke Kuper, Josué Alejandro Huertas Guzmán, Harry Wichers, Thomas Keil, A. Haddi, Jennifer Santos, Regina Selb, Aida del Campo García, Maria Basagaña, Valentino Pavišić, Angela Simpson, Chris H. Bridts, Susana Piedade, Silvia Gallina, Isabella Pali-Schöll, Inês Pádua, Margaretha A. Faber, Frédéric de Blay, Luís Câmara Pestana, Ben Remington, Anna S. Pelkonen, Sandra Lucarelli, Ivana Šutić, Olivier Tranquet, Montserrat López Onieva, Antonio Amoroso, Paola Minale, Katia Basello, George Du Toit, Daniela Adriano, Adnan Custovic, Zbikowska-Gotz M, Domingo Barber, Inmaculada Doña, Christine Breynaert, Hanan Sharif, Manon M. Oude Nijhuis, Sandra Denery, Bertine M. J. Flokstra-de Blok, Rinkesh Kumar Gupta, Pieter-Jan de Kam, Dianne E. Campbell, Carmen M. D'Amelio, Nunzia Maiello, Ingo Marenholz, José María Ignacio García, Helen Lindqvist, Lilian Moraes, Cleonir Lui de Moraes Beck, Eunice Dias de Castro, Cono Casale, Barbara Majkowska-Wojciechowska, Maria Petrodimopoulou, Andrea Mikkelsen, Hub P. J. M. Noteborn, Hulya Ercan Saricoban, Moira Austin, Martinus Løvik, Graham Roberts, Isabella Annesi-Maesano, Aeilko H. Zwinderman, Sigrun H. Lund, Anouska D. Michelsen-Huisman, Fernando Bandrés Sánchez-Cruz, Francisco Javier Ruano, Valérie Liabeuf, Eman Madbouly, Pasquale Comberiati, Maria Isabel Garcimartin, Stephan Scheurer, Inna A. Larkova, Jean Tratt, Renata Rodrigues Cocco, Younes Belabbas, Lorella Paparo, Elizabeth Griffiths, Gian Lodovico Rapaccini, Audrey Dunn Galvin, Zizi Cojocariu, Isidor Hutteger, Claire Claverie, S.M. Nedelska, Anna Kuklinska-Pijanka, Jenny Badas, Mónica Piquer, Iztok Devetak, A.K.F. Gushken, Frans Timmermans, Adriana Machinena, Francisco Javier Monteseirin, Amaranta Traversa, Fátima Cabral Duarte, Tomaž Poredoš, Peter Meyer, Cristina Arêde, Rosa Muñoz-Cano, Barbara Pfitzner, Alejandro Joral, Juan Carlos Daza, Laurent L. Reber, Olga Chernyak, and Maria Antonetta Ciardiello

Subjects
Pulmonary and Respiratory Medicine, Allergy, medicine.medical_specialty, 030504 nursing, business.industry, Immunology, RC581-607, medicine.disease, Meeting Abstracts, 03 medical and health sciences, 0302 clinical medicine, Food allergy, 030225 pediatrics, Family medicine, medicine, Immunology and Allergy, Immunologic diseases. Allergy, 0305 other medical science, business, Anaphylaxis
Published
2017
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10. A role for Peroxisome Proliferator-Activated Receptor Beta in T cell development

Author

I. Mothe-Satney, B. Sibille, Frédéric Larbret, Akila Rekima, Joseph Murdaca, Gwenaëlle Le Menn, Raphaëlle Squillace, Juline Pelé, Paul A. Grimaldi, Anne Sophie Rousseau, Jaap G Neels, and Valérie Verhasselt

Subjects
0301 basic medicine, Multidisciplinary, ZAP70, T cell, CD28, Biology, Natural killer T cell, Article, Cell biology, 03 medical and health sciences, Interleukin 21, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Biochemistry, medicine, Cytotoxic T cell, IL-2 receptor, Antigen-presenting cell, 030215 immunology
Abstract

Metabolism plays an important role in T cell biology and changes in metabolism drive T cell differentiation and fate. Most research on the role of metabolism in T lymphocytes focuses on mature T cells while only few studies have investigated the role of metabolism in T cell development. In this study, we report that activation or overexpression of the transcription factor Peroxisome Proliferator-Activated Receptor β (PPARβ) increases fatty acid oxidation in T cells. Furthermore, using both in vivo and in vitro models, we demonstrate that PPARβ activation/overexpression inhibits thymic T cell development by decreasing proliferation of CD4−CD8− double-negative stage 4 (DN4) thymocytes. These results support a model where PPARβ activation/overexpression favours fatty acid- instead of glucose-oxidation in developing T cells, thereby hampering the proliferative burst normally occurring at the DN4 stage of T cell development. As a consequence, the αβ T cells that are derived from DN4 thymocytes are dramatically decreased in peripheral lymphoid tissues, while the γδ T cell population remains untouched. This is the first report of a direct role for a member of the PPAR family of nuclear receptors in the development of T cells.

Published
2016

11. L’allaitement maternel peut-il prévenir les maladies allergiques par l’induction de tolérance orale ?

Author

Akila Rekima, Meri K. Tulic, Valérie Verhasselt, and Patricia Macchiaverni

Subjects
Gynecology, medicine.medical_specialty, business.industry, Primary prevention, medicine, Immunology and Allergy, business
Abstract

Resume Le systeme immunitaire du nouveau-ne est soumis a un defi considerable devant a la fois faire face a une stimulation antigenique massive du fait de la colonisation microbienne de la peau et du tractus digestif ainsi que de l’exposition a une multitude d’antigenes environnementaux. Outre ses vertus nutritives et son impact sur la prevention des maladies infectieuses, le lait maternel pourrait contribuer a l’education du systeme immunitaire vers l’acceptation des antigenes du soi et de l’environnement inoffensifs. En effet, des etudes epidemiologiques rapportent un effet protecteur de l’allaitement vis-a-vis de maladies dues a un defaut de tolerance immunitaire, telles que le diabete de type 1, la maladie cœliaque et les allergies. Cependant, les donnees de la litterature sont controversees et les mecanismes peu identifies. Dans cette revue, nous presenterons et discuterons les donnees qui suggerent que l’allaitement pourrait exercer des effets protecteurs a l’egard des maladies allergiques par induction de tolerance immunitaire suite au transfert d’allergene dans le lait. Nous presenterons les facteurs requis pour conferer ce potentiel tolerogene au lait maternel. Une meilleure comprehension des mecanismes de tolerance en debut de vie et de l’impact de la mere sur ce processus via l’allaitement devrait permettre de proposer de nouvelles strategies de prevention des maladies allergiques.

Published
2012
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12. Oral tolerance is inefficient in neonatal mice due to a physiological vitamin A deficiency

Author

L Le Bourhis, G. R. van den Brink, Akila Rekima, M. Turfkruyer, Valérie Verhasselt, Vanesa Muncan, Patricia Macchiaverni, Meri K. Tulic, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Gastroenterology and Hepatology, AII - Amsterdam institute for Infection and Immunity, and Tytgat Institute for Liver and Intestinal Research

Subjects
0301 basic medicine, Vitamin, business.industry, Immunology, Inflammation, Breast milk, medicine.disease, Immune tolerance, Vitamin A deficiency, 03 medical and health sciences, chemistry.chemical_compound, Tolerance induction, 030104 developmental biology, 0302 clinical medicine, chemistry, Immunity, medicine, Immunology and Allergy, medicine.symptom, business, Neonatal stage, 030215 immunology
Abstract

Increased risk of allergy during early life indicates deficient immune regulation in this period of life. To date, the cause for inefficient neonatal immune regulation has never been elucidated. We aimed to define the ontogeny of oral tolerance and to identify necessary conditions specific for this stage of life. Ovalbumin (OVA) was administered orally to mice through breast milk and efficiency of systemic tolerance to OVA was assessed in adulthood using a model of allergic airway inflammation. Oral tolerance induction was fully efficient starting third week of life. Inefficiency in neonates was a consequence of abnormal antigen transfer across the gut barrier and retinaldehyde dehydrogenase expression by mesenteric lymph node CD103(+) neonatal dendritic cells, resulting in inefficient T-cell activation. Neonates' serum retinol levels were three times lower than in adult mice, and vitamin A supplementation was sufficient to rescue neonatal defects and allow tolerance induction from birth. The establishment of oral tolerance required the differentiation of Th1 lymphocytes in both vitamin A-supplemented neonates and 3-week-old unsupplemented mice. This knowledge should guide the design of interventions for allergy prevention that are adapted to the neonatal stage of life such as vitamin A supplementation.

Published
2016

13. Respiratory allergen from house dust mite is present in human milk and primes for allergic sensitization in a mouse model of asthma

Author

Laurent Mascarell, Susan L. Prescott, Karine Adel-Patient, Sabi Airouche, Patricia Macchiaverni, Philippe Moingeon, M. Turfkruyer, Valérie Verhasselt, Meri K. Tulic, Isabella Annesi-Maesano, Antonio Condino-Neto, Akila Rekima, Institute of Biomedical Sciences, Universidad de Chile = University of Chile [Santiago] (UCHILE), Université de Nice Sophia-Antipolis (UNSA), Stallergenes, Unité de Recherche Immuno-Allergie Alimentaire, Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), School of Pediatrics and Child Health, The University of Western Australia (UWA), The International Inflammation 'in-FLAME' Network, Worldwide Universities Network (WUN), Institut National de la Sante et Recherche Medicale (INSERM), Universite de Nice Sophia-Antipolis, Societe Francaise d'Allergologie (SFA), Fond de Recherche en Sante Respiratoire, Fondation Princesse Grace, and Sao Paulo Research Foundation (FAPESP) [2012/51290-6]

Subjects
Allergy, [SDV]Life Sciences [q-bio], Immunology, human breast milk, allergic sensitization, Breast milk, medicine.disease_cause, Arthropod Proteins, Allergic sensitization, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Allergen, Antigen, Pregnancy, medicine, Immunology and Allergy, Animals, Humans, allergy primary prevention, Antigens, Dermatophagoides, house dust mite, IMUNOLOGIA, Sensitization, Asthma, House dust mite, biology, Milk, Human, business.industry, Colostrum, Pyroglyphidae, food and beverages, Environmental exposure, Environmental Exposure, Allergens, biology.organism_classification, medicine.disease, 3. Good health, Cysteine Endopeptidases, medicine.anatomical_structure, 030228 respiratory system, Female, neonatal oral immune tolerance, business
Abstract

International audience; Introduction.– Impact of exposure to environmental allergens during early life on allergic sensitization and disease development is controversial. Here, we investigated whether airborne allergen from Dermatophagoides pteronyssinus (Der p) house dust mite (HDM), a major cause of allergic asthma, is found in human colostrum and milk samples and set up a mouse model to assess its impact on allergic outcome in offspring. Methods.– Der p 1was quantified in human milk (1 and 6 months postpartum samples from Australia, n = 71 and n = 161, respectively) and colostrum from Brasil (n = 76), France (n = 97) and Australia (n = 34) by ELISA. A basophil degranulation assay was used to confirm immunogenicity of ELISA-detected Der p. Balb/c mice were fostered by mothers exposed intra-nasally to Der p extract before pregnancy and during lactation. Progeny response to Der p was measured at 6 weeks and included assessment of allergic sensitization, airway inflammation and lungs function. Results.– Der p 1 was present in 58% Brazilian, 70% French, and 78% Australian colostrum. Median [Der p 1] was similar between countries (96 pg/mL; IQR 50.2–201.6 pg/mL). In mature milk, Der p1 was found in 52% of 1-month and 6-month samples. Median [Der p 1] in milk was 65.9 pg/mL; IQR 41.5–172 pg/mL) and was significantly lower than in colostrum (P = 0.0001). Der p 1-containing milks were able to induce degranulation of human anti-Der p IgE coated basophils. Mice breastfed by Der p-exposed mothers had 5-fold increased levels of Der p specific IgE and IgG1 compared to mice breastfed by naïve mothers and their allergic airway inflammation and lung function was not affected. Conclusion.– This study demonstrates that early life exposure to ubiquitous respiratory allergens can take place through breastfeeding. An animal model mimicking the human situation shows early life exposure to Der p through milk primes the immune system rather than protect it as we reported with OVA. These data highlight that antigen administration to the neonate through the oral route may contribute to child allergic sensitization and have important implications for the design of studies assessing early oral antigen exposure for allergic disease prevention.

Published
2014
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14. Early oral exposure to house dust mite allergen through breast milk: A potential risk factor for allergic sensitization and respiratory allergies in children

Author

Nour Baïz, Patricia Macchiaverni, Meri K. Tulic, Akila Rekima, Isabella Annesi-Maesano, Valérie Verhasselt, I. Annesi-Maesano, J.Y. Bernard, J. Botton, M.A. Charles, P. Dargent-Molina, B. de Lauzon-Guillain, P. Ducimetière, M. de Agostini, B. Foliguet, A. Forhan, X. Fritel, A. Germa, V. Goua, R. Hankard, B. Heude, M. Kaminski, B. Larroque, N. Lelong, J. Lepeule, G. Magnin, F. Pierre, L. Marchand, C. Nabet, R. Slama, M.J. Saurel-Cubizolles, M. Schweitzer, and O. Thiebaugeorges

Subjects
0301 basic medicine, Allergy, House dust mite allergen, business.industry, Potential risk, Immunology, Breast milk, medicine.disease, Allergic sensitization, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030228 respiratory system, medicine, Immunology and Allergy, Respiratory system, business, Prospective cohort study, Breast feeding
Published
2017
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15. Breast milk immune complexes are potent inducers of oral tolerance in neonates and prevent asthma development

Author

Eric Mosconi, Akira Kanda, Barbara Seitz-Polski, Sébastien Fleury, Akila Rekima, Nicolas Glaichenhaus, Valérie Verhasselt, Renato C. Monteiro, Valérie Julia, David Dombrowicz, Emilie Tissandie, Immunologie des maladies infectieuses allergiques et autoimmunes, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Schistosomiase, paludisme et inflammation, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Université Lille Nord de France (COMUE), Réseau International des Instituts Pasteur (RIIP), Immunopathologie rénale, récepteurs et inflammation, and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Asthma, MESH: Interleukin-2 Receptor alpha Subunit, Administration, Oral, Antigen-Antibody Complex, Receptors, Fc, T-Lymphocytes, Regulatory, MESH: Mice, Knockout, MESH: Animals, Newborn, MESH: Histocompatibility Antigens Class I, Mice, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, Immunology and Allergy, MESH: Animals, IL-2 receptor, MESH: Maternal Exposure, Mice, Knockout, MESH: Immunoglobulin G, Mice, Inbred BALB C, 0303 health sciences, MESH: Milk, Human, FOXP3, Forkhead Transcription Factors, MESH: Antigen-Antibody Complex, 3. Good health, Tolerance induction, Breast Feeding, Maternal Exposure, MESH: Breast Feeding, MESH: Administration, Oral, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Receptors, Fc, MESH: Allergens, MESH: Immune Tolerance, Ovalbumin, Immunology, MESH: Mice, Inbred BALB C, Breast milk, 03 medical and health sciences, Immune system, Neonatal Fc receptor, Antigen, MESH: Mice, Inbred C57BL, MESH: Forkhead Transcription Factors, Immune Tolerance, medicine, Animals, MESH: Mice, 030304 developmental biology, Asthma, MESH: Ovalbumin, Milk, Human, business.industry, MESH: T-Lymphocytes, Regulatory, Histocompatibility Antigens Class I, Interleukin-2 Receptor alpha Subunit, Allergens, medicine.disease, MESH: Male, Mice, Inbred C57BL, Animals, Newborn, Immunoglobulin G, MESH: Immunity, Maternally-Acquired, business, Immunity, Maternally-Acquired, MESH: Female, 030215 immunology
Abstract

International audience; Allergic asthma is a chronic lung disease resulting from an inappropriate T helper (Th)-2 response to environmental antigens. Early tolerance induction is an attractive approach for primary prevention of asthma. Here, we found that breastfeeding by antigen-sensitized mothers exposed to antigen aerosols during lactation induced a robust and long-lasting antigen-specific protection from asthma. Protection was more profound and persistent than the one induced by antigen-exposed non-sensitized mothers. Milk from antigen-exposed sensitized mothers contained antigen-immunoglobulin (Ig) G immune complexes that were transferred to the newborn through the neonatal Fc receptor resulting in the induction of antigen-specific FoxP3(+) CD25(+) regulatory T cells. The induction of oral tolerance by milk immune complexes did not require the presence of transforming growth factor-beta in milk in contrast to tolerance induced by milk-borne free antigen. Furthermore, neither the presence of IgA in milk nor the expression of the inhibitory FcgammaRIIb in the newborn was required for tolerance induction. This study provides new insights on the mechanisms of tolerance induction in neonates and highlights that IgG immune complexes found in breast milk are potent inducers of oral tolerance. These observations may pave the way for the identification of key factors for primary prevention of immune-mediated diseases such as asthma.

Published
2010
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17. PD01 - Respiratory allergens in human milk: potential impact on susceptibility to allergic airway disease

Author

Philippe Moingeon, Isabella Annesi-Maesano, M. Turfkruyer, Karine Adel-Patient, Antonio Condino-Neto, Sabi Airouche, Laurent Mascarell, Valérie Verhasselt, Susan L. Prescott, Patricia Macchiaverni, Meri K. Tulic, Akila Rekima, BMC, Ed., Institute of Biomedical Sciences, Universidade de São Paulo = University of São Paulo (USP), Tolérance Immunitaire (EA 6302), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Research and Development, Stallergenes SA, Unité d'Immuno-Allergie Alimentaire (UIAA - UR 496), Institut National de la Recherche Agronomique (INRA), Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), School of Pediatrics and Child Health, The University of Western Australia (UWA), The International Inflammation 'in-FLAME' Network, and Worldwide Universities Network (WUN)

Subjects
Pulmonary and Respiratory Medicine, Potential impact, Allergy, biology, Allergic airway inflammation, [SDV.IMM] Life Sciences [q-bio]/Immunology, business.industry, Immunology, Degranulation, Immunoglobulin E, medicine.disease, Airway disease, biology.protein, Immunology and Allergy, Medicine, Colostrum, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMethodologies_GENERAL, Poster Discussion Presentation, Respiratory system, business, ComputingMilieux_MISCELLANEOUS
Abstract

Results Der p 1 was present in 58% Brazilian, 70% French, and 78% Australian colostrum. Median [Der p 1] was similar between countries (96 pg/mL). In mature milk, Der p1 was found in 55% of samples, median [Der p 1] was 65·9 pg/mL and was significantly lower than in colostrum (p=0·0001). Der p 1-containing milks were able to induce basophils degranulation. Mice breastfed by Der p-exposed mothers had 5-fold increased levels of Der p specific IgE and IgG1 compared to mice breastfed by naive mothers. Their allergic airway inflammation was not affected.

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