Increased adaptive immune responses and proper feedback regulation protect against clinical dengue
| Autor: | Anavaj Sakuntabhai, Arnaud Tarantola, Veasna Duong, Philippe Buchy, Noémie Courtejoie, Philippe Dussart, Ahmed Tawfik, Sivlin Ung, Kevin Bleakley, Etienne Simon-Loriere, Sowath Ly, Matthieu Prot, Isabelle Casademont, Tineke Cantaert |
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| Přispěvatelé: | Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Unité d'Épidémiologie et de Santé Publique [Phnom Penh], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratoire de Mathématiques d'Orsay (LM-Orsay), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria), GlaxoSmithKline, Glaxo Smith Kline, Unité de Virologie / Virology Unit [Phnom Penh], This work was supported by the European Union Seventh Framework Programme (FP7/2007-2011) under grant agreement 282378 and the PTR373 funding of Institut Pasteur International Network., European Project: 282378, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Génétique fonctionnelle des Maladies infectieuses, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur du Cambodge-Réseau International des Instituts Pasteur ( RIIP ), Unité d'Épidémiologie et de Santé Publique, Institut National de Recherche en Informatique et en Automatique ( Inria ), Département de Mathématiques [ORSAY], Université Paris-Sud - Paris 11 ( UP11 ), GlaxoSmithKline (GSK) Vaccine, European Project : 282378, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MESH: Inflammation Transcription Genetic MESH: Feedback Physiological T-Lymphocytes viruses Apoptosis MESH: Dengue Adaptive Immunity Dengue virus Antibodies Viral Lymphocyte Activation medicine.disease_cause Dengue fever Dengue 0302 clinical medicine [STAT.ML]Statistics [stat]/Machine Learning [stat.ML] MESH: Demography [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Child [ SDV.IMM ] Life Sciences [q-bio]/Immunology Child MESH: Treatment Outcome Feedback Physiological Antigen Presentation education.field_of_study MESH: Cytokines MESH: Plasma Cells Cell Differentiation General Medicine Viral Load MESH: Gene Expression Regulation 3. Good health [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases Treatment Outcome medicine.anatomical_structure [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology Acute Disease Cytokines MESH: Acute Disease MESH: Immunity Innate medicine.symptom MESH: Viral Load Viral load MESH: Cell Differentiation T cell Plasma Cells 030231 tropical medicine Population Asymptomatic 03 medical and health sciences Immune system medicine Humans Viremia MESH: Viremia Quantitative Biology - Populations and Evolution education MESH: Lymphocyte Activation Demography Inflammation Innate immune system MESH: Humans [ SDV ] Life Sciences [q-bio] business.industry MESH: Transcription Genetic MESH: Apoptosis Populations and Evolution (q-bio.PE) biochemical phenomena metabolism and nutrition medicine.disease Immunity Innate 030104 developmental biology MESH: T-Lymphocytes Gene Expression Regulation FOS: Biological sciences Immunology MESH: Antigen Presentation business MESH: Adaptive Immunity MESH: Antibodies Viral |
| Zdroj: | Science Translational Medicine Science Translational Medicine, American Association for the Advancement of Science, 2017, 9 (405), pp.eaal5088. ⟨10.1126/scitranslmed.aal5088⟩ Science Translational Medicine, 2017, 9 (405), pp.eaal5088. ⟨10.1126/scitranslmed.aal5088⟩ Science Translational Medicine, American Association for the Advancement of Science, 2017, 9 (405), 〈10.1126/scitranslmed.aal5088〉 |
| ISSN: | 1946-6234 1946-6242 |
| Popis: | International audience; Clinical symptoms of dengue virus (DENV) infection, the most prevalent arthropod-borne viral disease, range from classical mild dengue fever to severe, life-threatening dengue shock syndrome. However, most DENV infections cause few or no symptoms. Asymptomatic DENV-infected patients provide a unique opportunity to decipher the host immune responses leading to virus elimination without negative impact on an individual's health. We used an integrated approach of transcriptional profiling and immunological analysis to compare a Cambodian population of strictly asymptomatic viremic individuals with clinical dengue patients. Whereas inflammatory pathways and innate immune response pathways were similar between asymptomatic individuals and clinical dengue patients, expression of proteins related to antigen presentation and subsequent T cell and B cell activation pathways was differentially regulated, independent of viral load and previous DENV infection history. Feedback mechanisms controlled the immune response in asymptomatic viremic individuals, as demonstrated by increased activation of T cell apoptosis-related pathways and FcγRIIB (Fcγ receptor IIB) signaling associated with decreased anti-DENV-specific antibody concentrations. Together, our data illustrate that symptom-free DENV infection in children is associated with increased activation of the adaptive immune compartment and proper control mechanisms, leading to elimination of viral infection without excessive immune activation, with implications for novel vaccine development strategies. |
| Databáze: | OpenAIRE |
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