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Manon Levêque,1 Nadim Cassir,2 Fanny Mathias,3 Cindy Fevre,4 Florence Daviet,5 Julien Bermudez,1 Geoffrey Brioude,6 Florence Peyron,3 Martine Reynaud-Gaubert,1 Benjamin Coiffard1 1Department of Respiratory Medicine and Lung Transplantation, APHM, Aix Marseille University, Hôpital Nord, Marseille, France; 2Department of Infectious Disease, APHM, IHU Méditerranée Infection, Aix-Marseille University, Marseille, France; 3Department of Pharmacy, APHM, Aix Marseille University, Hôpital Nord, Marseille, France; 4Research and Development, Pherecydes Pharma, Romainville, France; 5Intensive Care Medicine, APHM, Aix Marseille University, Hôpital Nord, Marseille, France; 6Department of Thoracic Surgery and Lung Transplantation, APHM, Aix Marseille University, Hôpital Nord, Marseille, FranceCorrespondence: Benjamin Coiffard, Department of Respiratory Medicine and Lung Transplantation, APHM, CHU Nord, Chemin des Bourrely, Marseille, 13915, France, Tel +33491966133, Email benjamin.coiffard@ap-hm.frAbstract: Recipients transplanted for bronchiectasis in the context of a primary immune deficiency, such as common variable immunodeficiency, are at a high risk of severe infection in post-transplantation leading to poorer long-term outcomes than other transplant indications. In this report, we present a fatal case due to chronic Pseudomonas aeruginosa bronchopulmonary infection in a lung transplant recipient with common variable immunodeficiency despite successful eradication of an extensively drug-resistant (XDR) strain with IgM/IgA-enriched immunoglobulins and bacteriophage therapy. The fatal evolution despite a drastic adaptation of the immunosuppressive regimen and the maximal antibiotic therapy strategy raises the question of the contraindication of lung transplantation in such a context of primary immunodeficiency.Keywords: primary immunodeficiency diseases, lung transplantation, Pseudomonas aeruginosa, phage therapy, immunoglobulin therapy

Marie-Françoise Aries,1 Hélène Hernandez-Pigeon,1 Clémence Vaissière,1 Hélène Delga,1 Antony Caruana,1 Marguerite Lévêque,1 Muriel Bourrain,1,2 Katia Ravard Helffer,1 Bertrand Chol,3 Thien Nguyen,1 Sandrine Bessou-Touya,1 Nathalie Castex-Rizzi1 1Pierre Fabre Dermo-Cosmétique, Centre de Recherche & Développement Pierre Fabre, Toulouse, 2Sorbonne Universités, UPMC Univ Paris 06, CNRS, Laboratoire de Biodiversité et Biotechnologies Microbiennes (LBBM), Observatoire Océanologique, Banyuls/Mer, France; 3Centre d’Immunologie Pierre Fabre, Saint-Julien-en-Genevois, France Background: Atopic dermatitis (AD) is a common skin disease characterized by recurrent pruritic inflammatory skin lesions resulting from structural and immune defects of the skin barrier. Previous studies have shown the clinical efficacy of Avène thermal spring water in AD, and a new microorganism, Aquaphilus dolomiae was suspected to contribute to these unique properties. The present study evaluated the anti-inflammatory, antipruritic, and immunomodulatory properties of ES0, an original biological extract of A. dolomiae, in immune and inflammatory cell models in order to assess its potential use in the treatment of AD.Materials and methods: An ES0 extract containing periplasmic and membrane proteins, peptides, lipopolysaccharides, and exopolysaccharides was obtained from A. dolomiae. The effects of the extract on pruritus and inflammatory mediators and immune mechanisms were evaluated by using various AD cell models and assays.Results: In a keratinocyte model, ES0 inhibited the expression of the inflammatory mediators, thymic stromal lymphopoietin, interleukin (IL)-18, IL-4R, IL-8, monocyte chemoattractant protein-3, macrophage inflammatory protein-3α, and macrophage-derived chemokine and induced the expression of involucrin, which is involved in skin barrier keratinocyte terminal differentiation. In addition, ES0 inhibited protease-activated receptor-2 activation in HaCaT human keratinocytes stimulated by stratum corneum tryptic enzyme and T helper type (Th) 1, Th2, and Th17 cytokine production in Staphylococcal enterotoxin B–stimulated CD4+ lymphocytes. Lastly, ES0 markedly activated innate immunity through toll-like receptor (TLR) 2, TLR4, and TLR5 activation (in recombinant human embryonic kidney 293 cells) and through antimicrobial peptide induction (psoriasin, human beta-defensin-2, and cathelicidin), mainly through TLR5 activation (in normal human keratinocytes).Conclusion: Overall, these in vitro results confirm the marked regulatory activity of this A. dolomiae extract on inflammatory and immune responses, which may be of value by virtue of its potential as an adjunctive treatment of AD inflammatory and pruritic lesions. Keywords: atopic dermatitis, inflammation, anti-inflammation, in vitro and in vivo activities, barrier function, microorganism