Plasminogen controls inflammation and pathogenesis of influenza virus infections via fibrinolysis
| Autor: | Stella E. Vogelzang-van Trierum, Vuong Ba Lê, Bruno Lina, Peter Carmeliet, Roger Lijnen, Fatima Berri, Michel Hanss, Eric Camerer, Guus F. Rimmelzwaan, Emmanuel Albina, Marie-Laure Foucault-Grunenwald, Dominique Martinez, Patricia Gil, Béatrice Riteau |
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| Přispěvatelé: | Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dept Virol, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospices Civils de Lyon (HCL), Contrôle des maladies animales exotiques et émergentes (UMR CMAEE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Université Catholique de Louvain = Catholic University of Louvain (UCL), Flanders Institute for Biotechnology, Département Santé Animale (DEPT SA), Institut National de la Recherche Agronomique (INRA), Agence Nationale de la Recherche (ANR), Long term Structural funding - Methusalem by the Flemish Government, INSERM avenir, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Virology |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Pulmonology medicine.medical_treatment [SDV]Life Sciences [q-bio] 030204 cardiovascular system & hematology medicine.disease_cause L73 - Maladies des animaux Virus Replication Fibrinogène Pathogenesis Pathogénèse Mice 0302 clinical medicine Influenza A Virus H1N1 Subtype Influenza A virus Coagulation sanguine Biology (General) Mice Knockout 0303 health sciences Fibrinolysis Hematology 3. Good health Host-Pathogen Interaction [SDV] Life Sciences [q-bio] Cytokine Expérimentation en laboratoire Host-Pathogen Interactions Medicine Female medicine.symptom Infection Fibrin Clot Lysis Time Research Article Souris QH301-705.5 Immunology Pneumonia Viral Inflammation Immunopathology Biology Microbiology Antiviral Agents Virus Immunomodulation 03 medical and health sciences Fibrinolytic Agents Orthomyxoviridae Infections Virology Genetics medicine Animals Influenzavirus aviaire Molecular Biology 030304 developmental biology Fibrin Influenza A Virus H5N1 Subtype Fibrinogen Plasminogen RC581-607 Influenza A virus subtype H5N1 Mice Inbred C57BL Poumon Parasitology Immunologic diseases. Allergy Fibrinolytic agent |
| Zdroj: | PLoS Pathogens PLoS Pathogens, 2013, 9 (3), ⟨10.1371/journal.ppat.1003229⟩ Plos Pathogens 3 (9), . (2013) PLoS Pathogens, Public Library of Science, 2013, 9 (3), ⟨10.1371/journal.ppat.1003229⟩ PLoS Pathogens (print), 9(3). Public Library of Science PLoS Pathogens, Vol 9, Iss 3, p e1003229 (2013) |
| ISSN: | 1553-7366 1553-7374 |
| DOI: | 10.1371/journal.ppat.1003229⟩ |
| Popis: | Detrimental inflammation of the lungs is a hallmark of severe influenza virus infections. Endothelial cells are the source of cytokine amplification, although mechanisms underlying this process are unknown. Here, using combined pharmacological and gene-deletion approaches, we show that plasminogen controls lung inflammation and pathogenesis of infections with influenza A/PR/8/34, highly pathogenic H5N1 and 2009 pandemic H1N1 viruses. Reduction of virus replication was not responsible for the observed effect. However, pharmacological depletion of fibrinogen, the main target of plasminogen reversed disease resistance of plasminogen-deficient mice or mice treated with an inhibitor of plasminogen-mediated fibrinolysis. Therefore, plasminogen contributes to the deleterious inflammation of the lungs and local fibrin clot formation may be implicated in host defense against influenza virus infections. Our studies suggest that the hemostatic system might be explored for novel treatments against influenza. Author Summary Influenza viruses, including H5N1 bird influenza viruses continue to form a major threat for public health. Available antiviral drugs for the treatment of influenza are effective to a limited extent and the emergence of resistant viruses may further undermine their use. The symptoms associated with influenza are caused by replication of the virus in the respiratory tract and the host immune response. Here, we report that a molecule of the fibrinolytic system, plasminogen, contributes to inflammation caused by influenza. Inhibiting the action of plasminogen protected mice from severe influenza infections, including those caused by H5N1 and H1N1 pandemic 2009 viruses and may be a promising novel strategy to treat influenza. |
| Databáze: | OpenAIRE |
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