X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production
| Autor: | Anne Durandy, Guillaume Vogt, Ludovic de Beaucoudrey, Cheng-Lung Ku, Anne Puel, Jalel Chemli, Necil Kutukculer, Emilie Vinolo, Claire Fieschi, Christine Bodemer, Alessandro Plebani, Karin Christel, Brigitte Senechal, Laurent Abel, David M. Frucht, Klaus Magdorf, Capucine Picard, Michel Veron, Ariane Chapgier, Meriem Garfa, Horst von Bernuth, Ridha Barbouche, Maria Tsolia, Emmanuelle Jouanguy, Margje H. Haverkamp, Alain Israël, Jacinta Bustamante, Fabrice Agou, Maike Knackstedt, Frederic Geissmann, Steven M. Holland, Jacqueline Feinberg, Jean-Laurent Casanova, Luigi D. Notarangelo, Orchidée Filipe-Santos, Mohamed Bejaoui, Dominique Gendrel |
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| Přispěvatelé: | Ege Üniversitesi, Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of clinical infectious diseases, National Institutes of Health [Bethesda] (NIH), Department of Infectious Diseases, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Régulation Enzymatique des Activités Cellulaires, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratory of Cell Biology, Center for Drug Evaluation and Research (CDER)-U.S. Food and Drug Administration (FDA), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Système des phagocytes mononucléés et immunopathologie, Université Paris Descartes - Paris 5 (UPD5), Laboratoire d'immunologie, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Microscopie confocale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Departement de Pediatrie, hôpital Sahloul, Centre National de Greffe de la Moëlle osseuse Tunis (CNGMO), Second Department of Pediatrics, University of Athens School of Medicine-P. and A. Kyriakou Children's Hospital [Athens], Department of Pediatrics, Ege University, Università degli Studi di Brescia = University of Brescia (UniBs), Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Signalisation Moléculaire et Activation Cellulaire (SMAC), Department of Pediatric Pulmonology and Immunology, Virchow Klinikum, Laboratoire d'immunologie clinique [Institut Pasteur de Tunis], Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Département de Pédiatrie, Hôpital Saint Vincent de Paul, Service d'immuno-hématologie pédiatrique [CHU Necker], Aytac, Marie-Dominique, University of Athens School of Medicine-P. and A. Kyriakou Children's Hospital, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Brescia [Brescia], CHU Necker - Enfants Malades [AP-HP], Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), National Institutes of Health ( NIH ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Center for Drug Evaluation and Research-U.S. Food and Drug Administration ( FDA ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Centre National de greffe de moelle osseuse deTunis, Department of Pediatrics and Institute for Molecular Medicine Angello Nocivelli, University of Brescia, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Signalisation Moléculaire et Activation Cellulaire ( SMAC ), Institut Pasteur de Tunis-Réseau International des Instituts Pasteur ( RIIP ) |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Male
MESH: Interleukin-12 MESH : My MESH: My MESH : Child Preschool medicine.disease_cause Mice 0302 clinical medicine L Cells MESH : Child Interferon Genes X-Linked MESH: Child Immunology and Allergy MESH : Female MESH: Animals MESH : Antigens CD40 Child MESH: L Cells (Cell Line) Cells Cultured Cell Line Transformed 0303 health sciences Mutation biology MESH: Genetic Predisposition to Disease MESH : Cell Line Transformed MESH : Infant Articles MESH : Adult Interleukin-12 MESH: Infant 3. Good health I-kappa B Kinase Pedigree medicine.anatomical_structure Child Preschool Interleukin 12 Tumor necrosis factor alpha Female medicine.drug MESH: Cells Cultured Adult X Chromosome Adolescent MESH : Genes X-Linked MESH : L Cells (Cell Line) MESH : Male T cell Immunology Article MESH: Antigens CD40 03 medical and health sciences Germline mutation Antigen MESH : Adolescent MESH : Mice MESH : Cells Cultured MESH : Interleukin-12 medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Animals Humans Genetic Predisposition to Disease [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: I-kappa B Kinase MESH: Cell Line Transformed CD40 Antigens [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Mice 030304 developmental biology MESH: Adolescent Mycobacterium Infections CD40 MESH: Humans MESH : Humans MESH: Child Preschool Infant MESH : I-kappa B Kinase MESH: Adult Molecular biology MESH: Male MESH: Genes X-Linked biology.protein MESH : Genetic Predisposition to Disease MESH : Animals MESH: Female 030215 immunology |
| Zdroj: | Journal of Experimental Medicine Journal of Experimental Medicine, 2010, 203 (7), pp.1745-59. ⟨10.1084/jem.20060085⟩ The Journal of Experimental Medicine Journal of Experimental Medicine, Rockefeller University Press, 2010, 203 (7), pp.1745-59. ⟨10.1084/jem.20060085⟩ The Journal of Experimental Medecine The Journal of Experimental Medecine, The Rockefeller University Press, 2010, 203 (7), pp.1745-59. 〈10.1084/jem.20060085〉 |
| ISSN: | 0022-1007 1540-9538 |
| DOI: | 10.1084/jem.20060085⟩ |
| Popis: | WOS: 000238940500017 PubMed ID: 16818673 Germline mutations in five autosomal genes involved in interleukin (IL)-12-dependent, interferon (IFN)-gamma-mediated immunity cause Mendelian susceptibility to mycobacterial diseases (MSMD). The molecular basis of X-linked recessive (XR)-MSMD remains unknown. We report here mutations in the leucine zipper (LZ) domain of the NF-kappa B essential modulator (NEMO) gene in three unrelated kindreds with XR-MSMD. The mutant proteins were produced in normal amounts in blood and fibroblastic cells. However, the patients' monocytes presented an intrinsic defect in T cell-dependent IL-12 production, resulting in defective IFN-gamma secretion by T cells. IL-12 production was also impaired as the result of a specific defect in NEMO- and NF-kappa B/c-Rel-mediated CD40 signaling after the stimulation of monocytes and dendritic cells by CD40L-expressing T cells and fibroblasts, respectively. However, the CD40-dependent up-regulation of costimulatory molecules of dendritic cells and the proliferation and immunoglobulin class switch of B cells were normal. Moreover, the patients' blood and fibroblastic cells responded to other NF-kappa B activators, such as tumor necrosis factor-alpha, IL-beta, and lipopolysaccharide. These two mutations in the NEMO LZ domain provide the first genetic etiology of XR-MSMD. They also demonstrate the importance of the T cell- and CD40L-triggered, CD40-, and NEMO/NF-kappa B/c-Rel-mediated induction of IL-12 by monocyte-derived cells for protective immunity to mycobacteria in humans. Intramural NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA; Medical Research CouncilMedical Research Council UK (MRC) [G0900867] |
| Databáze: | OpenAIRE |
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