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4 results on '"Barbara Misme-Aucouturier"'

1. Allergic Sensitization Driving Immune Phenotyping and Disease Severity in a Mouse Model of Asthma

Author

Eléonore Dijoux, Martin Klein, Barbara Misme-Aucouturier, Marie-Aude Cheminant, Marion de Carvalho, Louise Collin, Dorian Hassoun, Erwan Delage, Mathilde Gourdel, Gervaise Loirand, Vincent Sauzeau, Antoine Magnan, Grégory Bouchaud, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Foch [Suresnes], Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), The Mibiogate consortium and the Fondation du souffle, INRAe Transfert and the 'Institut de Recherche en Santé Respiratoire des Pays de La Loire' IRSRPL. The Genavie Foundation., and ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016)

Subjects
Pulmonary and Respiratory Medicine, endotypes, barrier integrity, Immunology, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Respiratory function, lung microbiota
Abstract

International audience; Purpose. Asthma is a frequent chronic inflammatory bronchial disease affecting more than 300 million patients worldwide, 70% of whom are secondary to allergy. The diversity of asthmatic endotypes contributes to their complexity. The inter-relationship between allergen and other exposure and the airway microbiome adds to the phenotypic diversity and defines the natural course of asthma. Here, we compared the mouse models of house dust mite (HDM)-induced allergic asthma. Allergic sensitization was performed via various routes and associated with outcomes.Methods: Mice were sensitized with HDM via the oral, nasal or percutaneous routes. Lung function, barrier integrity, immune response and microbiota composition were analyzed.Results: Severe impairment of respiratory function was observed in the mice sensitized by the nasal and cutaneous paths. It was associated with epithelial dysfunction characterized by an increased permeability secondary to junction protein disruption. Such sensitization paths induced a mixed eosinophilic and neutrophilic inflammatory response with high interleukin (IL)-17 airway secretion. In contrast, orally sensitized mice showed a mild impairment of respiratory function. Epithelial dysfunction was mild with increased mucus production, but preserved epithelial junctions. Regarding lung microbiota, sensitization provoked a significant loss of diversity. At the genus level, Cutibacterium, Acinetobacter, Streptococcus and Lactobacillus were found to be modulated according to the sensitization pathway. An increase in theanti-inflammatory microbiota metabolites was observed in the oral-sensitization group.Conclusions: Our study highlights the strong impact of the sensitization route on the pathophysiology and the critical phenotypic diversity of allergic asthma in a mouse model.

Published
2023
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2. Engineering a safe monoclonal anti‐human IL‐2 that is effective in a murine model of food allergy and asthma

Author

Marie-Aude Cheminant, Marie Wauters, Grégory Bouchaud, Marion De Carvalho, Barbara Misme-Aucouturier, Antoine Magnan, Olivier Tranquet, Martin Klein, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Antwerp University Hospital [Edegem] (UZA), Fondation du Souffle, Fond de Dotation de Recherche en Santé Respiratoire, INRAE Transfert, 'Institut de Recherche en Sante Respiratoire' IRSR., and ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016)

Subjects
Allergy, Immunology, Immunoglobulin E, T-Lymphocytes, Regulatory, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Immune tolerance, Mice, 03 medical and health sciences, 0302 clinical medicine, Food allergy, antibody, [SDV.IDA]Life Sciences [q-bio]/Food engineering, medicine, Animals, Humans, Immunology and Allergy, T lymphocytes, Lymphocytes, dendritic cells, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, 030304 developmental biology, 0303 health sciences, biology, business.industry, IL-2, Innate lymphoid cell, asthma, medicine.disease, Acquired immune system, allergy, Immunity, Innate, 3. Good health, Disease Models, Animal, Monoclonal, biology.protein, Interleukin-2, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, business, Food Hypersensitivity, 030215 immunology
Abstract

International audience; Background Regulatory T cells (Tregs) are known to protect against allergies. Moreover, the decrease in the frequency and efficiency of Tregs amplifies allergic symptoms. Aim This study investigated whether expanding Tregs in vivo with an IL-2/IL-2 antibody complex could be safe, well tolerated and efficient in a therapeutic setting in allergies. Methods We produced an anti-IL-2 antibody (1C6) and demonstrated that when it is complexed to human IL-2, it increases IL-2 efficiency to induce Tregs in vivo without any detectable side effects. Furthermore, the IL-2/1C6 complex induces an increase in Helios expression by Tregs, suggesting that it not only elevated Treg numbers but also boosted their functions. Using mouse models of house-dust-mite-induced airway inflammation and wheat-gliadin-induced food allergies, we investigated the therapeutic potential of the IL-2/1C6 complex in allergies. Results IL-2/1C6 treatment significantly reduced allergic symptoms, specific IgE production, the adaptive immune response and tissue damage. Interestingly, IL-2/1C6 treatment modulated innate lymphoid cells by increasing ILC2s in asthma and decreasing ILC3s in food allergies. Conclusion In conclusion,complexed IL-2/anti-IL-2 may restore Treg numbers and function in respiratory and food allergies, thereby improving allergic markers and symptoms. Our IL-2/anti-IL-2 complex offers new hope for reestablishing immune tolerance in patients with allergies.

Published
2021
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3. Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis

Author

Mickael Vourc'h, Marion Davieau, Jose A Villadangos, Antoine Roquilly, Hamish E G McWilliam, Vanessa Gauttier, Abderrahmane Sadek, Raphaël Cinotti, Alexis Broquet, Cédric Jacqueline, Cynthia Fourgeux, Alice Molle, Frédéric Altare, Nadege Marec, Karim Asehnoune, Jeremie Poschmann, Paul Rooze, Barbara Misme-Aucouturier, Tanguy Chaumette, Le Bihan, Sylvie, Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Anesthésie Réanimation chirurgicale [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], University of Melbourne, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Moulay Ismail (UMI), Plateforme CYTOCELL Nantes (CRCINA-CYTOCELL), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Host-Pathogen Interactions in the Regulation of Immune Responses (CRCINA-ÉQUIPE 5), Dendritic cells and immunoregulation in transplantation and immunopathology (Team 1 - U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
0301 basic medicine, Phagocytosis, [SDV]Life Sciences [q-bio], Immunology, Inflammation, Systemic inflammation, Immune tolerance, Sepsis, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, Lung, biology, business.industry, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Pneumonia, 030104 developmental biology, medicine.anatomical_structure, biology.protein, medicine.symptom, Antibody, business, 030215 immunology
Abstract

International audience; Sepsis and trauma cause inflammation and elevated susceptibility to hospital-acquired pneumonia. As phagocytosis by macrophages plays a critical role in the control of bacteria, we investigated the phagocytic activity of macrophages after resolution of inflammation. After resolution of primary pneumonia, murine alveolar macrophages (AMs) exhibited poor phagocytic capacity for several weeks. These paralyzed AMs developed from resident AMs that underwent an epigenetic program of tolerogenic training. Such adaptation was not induced by direct encounter of the pathogen but by secondary immunosuppressive signals established locally upon resolution of primary infection. Signal-regulatory protein α (SIRPα) played a critical role in the establishment of the microenvironment that induced tolerogenic training. In humans with systemic inflammation, AMs and also circulating monocytes still displayed alterations consistent with reprogramming six months after resolution of inflammation. Antibody blockade of SIRPα restored phagocytosis in monocytes of critically ill patients in vitro, which suggests a potential strategy to prevent hospital-acquired pneumonia.

Published
2020
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4. Double positive CD4+CD8+ T cells are part of the adaptive immune response against Candida albicans

Author

Marjorie Albassier, Nidia Alvarez-Rueda, Patrice Le Pape, Adel Touahri, Francine Jotereau, Barbara Misme-Aucouturier, Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Nantes (UN)-Université de Nantes (UN)

Subjects
Adult, Male, 0301 basic medicine, CD8 Antigens, T-Lymphocytes, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, Inflammation, Adaptive Immunity, Lymphocyte Activation, Immunophenotyping, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Immune system, T-Lymphocyte Subsets, Candida albicans, medicine, Humans, Immunology and Allergy, Cytotoxic T cell, Cells, Cultured, biology, Candidiasis, General Medicine, Middle Aged, Acquired immune system, biology.organism_classification, 3. Good health, 030104 developmental biology, Cytokine, CD4 Antigens, Host-Pathogen Interactions, Cytokines, Female, Tumor necrosis factor alpha, medicine.symptom, CD8, 030215 immunology
Abstract

Although multiple immune cells participate in the innate and adaptive immune response against Candida albicans, the elucidation of cellular and inflammation kinetics may be a promising strategy to decipher events propitious to infection eradication. We used an in vitro Candida-human leucocyte coculture approach to study the dynamics of rare CD4+CD8+ double positive T lymphocytes (DP T) produced in response to this fungus. Our results highlight the presence of two phenotypically distinct subsets of DP T cells: CD4hiCD8lo and CD4loCD8hi, and that the different ratio of these cells correlates with infection outcome. The ratio of CD4hiCD8lo over CD4loCD8hi by day 6 was significantly higher in controlled infections and decreased when infection persisted due to a significant increase in the proportion of CD4loCD8hi. When infection was controlled, CD4hiCD8lo T cells secreted IFNγ, TNFα, IL-4 and IL-10 cytokines two days after challenge. By day 2, under conditions of persistent infection, CD4hiCD8lo and CD4loCD8hi T cells secreted significant levels of IL-4 and IL-10, respectively, compared to uninfected cultures. Frequency kinetics and original cytokine profiles detailed in this work indicate that DP T cells could participate in the adaptive immune response to C. albicans.

Published
2019
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