Selective predisposition to bacterial infections in IRAK-4–deficient children: IRAK-4–dependent TLRs are otherwise redundant in protective immunity
| العنوان: | Selective predisposition to bacterial infections in IRAK-4–deficient children: IRAK-4–dependent TLRs are otherwise redundant in protective immunity |
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| المؤلفون: | Sami Al-Hajjar, Carlos Rodríguez-Gallego, John I. Gallin, Toshiro Hara, Maya Chrabieh, Andrew C. Issekutz, Huey Hsuan Chang, Horst von Bernuth, Joanne Smart, Helen Chapel, Eric Vivier, László Maródi, David P. Speert, Mimi L.K. Tang, Jean-Laurent Casanova, Capucine Picard, Xiaoxia Li, Steven M. Holland, Shen-Ying Zhang, Franck J. Barrat, Stephan Ehl, Abdulaziz Al-Ghonaium, Ben Zion Garty, Chaim M. Roifman, Xavier Bossuyt, Douglas R. McDonald, Anne Puel, Hidetoshi Takada, Ofer Levy, Damien Sanlaville, Laurent Abel, Frederic Geissmann, Richard L. Miller, Cheng-Lung Ku, Kun Yang, Noorbibi K. Day-Good, Coleen K. Cunningham |
| المساهمون: | Génétique Humaine des Maladies Infectieuses (Inserm U980), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Interactions cellulaires neuroendocriniennes (ICN), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Interactions cellulaires neuroendocriniennes ( ICN ), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique ( CNRS ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of Groningen |
| المصدر: | The Journal of Experimental Medecine The Journal of Experimental Medecine, The Rockefeller University Press, 2007, 204 (10), pp.2407-22. ⟨10.1084/jem.20070628⟩ The Journal of Experimental Medecine, The Rockefeller University Press, 2007, 204 (10), pp.2407-22. 〈10.1084/jem.20070628〉 Journal of Experimental Medicine Journal of Experimental Medicine, Rockefeller University Press, 2007, 204 (10), pp.2407-22. ⟨10.1084/jem.20070628⟩ Journal of Experimental Medicine, 2007, 204 (10), pp.2407-22. ⟨10.1084/jem.20070628⟩ The Journal of Experimental Medicine Journal of Experimental Medicine, 204(10), 2407-2422. ROCKEFELLER UNIV PRESS |
| بيانات النشر: | Rockefeller University Press, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Male, Myeloid, Lipopolysaccharide, MESH : Cytokines, medicine.medical_treatment, MESH : Leukocytes, MESH : Child, Preschool, chemistry.chemical_compound, 0302 clinical medicine, MESH : Child, MESH: Child, Leukocytes, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Myeloid Cells, MESH : Female, Child, Cells, Cultured, MESH: Cytokines, 0303 health sciences, Toll-like receptor, MESH : Gene Expression Regulation, Interleukin, Cell Differentiation, PNEUMOCOCCAL MENINGITIS, MESH : Infant, Bacterial Infections, Articles, MYELOID DIFFERENTIATION FACTOR-88, MESH : Adult, MESH: Infant, MESH: Gene Expression Regulation, C-REACTIVE PROTEIN, Pedigree, 3. Good health, MESH : Bacterial Infections, Interleukin-1 Receptor-Associated Kinases, medicine.anatomical_structure, Cytokine, Child, Preschool, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Mutation, MESH : Cell Differentiation, IRAK4 KINASE-ACTIVITY, MESH: Toll-Like Receptors, MESH: Cells, Cultured, Adult, MESH: Cell Differentiation, MESH: Mutation, Adolescent, MESH : Myeloid Cells, MESH: Pedigree, MESH: Bacterial Infections, MESH : Male, Immunology, Biology, Article, MESH: Interleukin-1 Receptor-Associated Kinases, MESH: Leukocytes, IL-1 RECEPTOR, 03 medical and health sciences, Immunity, MESH : Adolescent, MESH : Cells, Cultured, medicine, Humans, 030304 developmental biology, TOLL-LIKE RECEPTORS, MESH: Adolescent, CUTTING EDGE, MESH: Humans, Innate immune system, MESH : Humans, MESH: Child, Preschool, HERPES-SIMPLEX-VIRUS, Infant, MESH: Adult, medicine.disease, MESH: Myeloid Cells, MESH: Male, Gene Expression Regulation, chemistry, MESH : Pedigree, MESH : Toll-Like Receptors, Mutation, PLASMACYTOID DENDRITIC CELLS, INNATE IMMUNITY, Primary immunodeficiency, MESH : Interleukin-1 Receptor-Associated Kinases, MESH: Female, 030215 immunology |
| الوصف: | Human interleukin ( IL) 1 receptor - associated kinase 4 ( IRAK- 4) deficiency is a recently discovered primary immunodefi ciency that impairs Toll/ IL- 1R immunity, except for the Toll- like receptor ( TLR) 3 - and TLR4 - interferon ( IFN)-alpha/beta pathways. The clinical and immunological phenotype remains largely unknown. We diagnosed up to 28 patients with IRAK- 4 deficiency, tested blood TLR responses for individual leukocyte subsets, and TLR responses for multiple cytokines. The patients' peripheral blood mononuclear cells ( PBMCs) did not induce the 11 non- IFN cytokines tested upon activation with TLR agonists other than the nonspecific TLR3 agonist poly( I: C). The patients' individual cell subsets from both myeloid ( granulocytes, monocytes, monocyte- derived dendritic cells [ MDDCs], myeloid DCs [ MDCs], and plasmacytoid DCs) and lymphoid ( B, T, and NK cells) lineages did not respond to the TLR agonists that stimulated control cells, with the exception of residual responses to poly( I: C) and lipopolysaccharide in MDCs and MDDCs. Most patients ( 22 out of 28; 79%) suffered from invasive pneumococcal disease, which was often recurrent ( 13 out of 22; 59%). Other infections were rare, with the exception of severe staphylococcal disease ( 9 out of 28; 32%). Almost half of the patients died ( 12 out of 28; 43%). No death and no invasive infection occurred in patients older than 8 and 14 yr, respectively. The IRAK- 4 - dependent TLRs and IL- 1Rs are therefore vital for childhood immunity to pyogenic bacteria, particularly Streptococcus pneumoniae. Conversely, IRAK- 4 - dependent human TLRs appear to play a redundant role in protective immunity to most infections, at most limited to childhood immunity to some pyogenic bacteria. |
| وصف الملف: | application/pdf |
| تدمد: | 1540-9538 0022-1007 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7099915ba0c10ec616712048d096eeb1Test https://doi.org/10.1084/jem.20070628Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7099915ba0c10ec616712048d096eeb1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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