Plasminogen controls inflammation and pathogenesis of influenza virus infections via fibrinolysis
Identifieur interne : 001197 ( Main/Merge ); précédent : 001196; suivant : 001198Plasminogen controls inflammation and pathogenesis of influenza virus infections via fibrinolysis
Auteurs : Fatma Berri [France] ; Guus F. Rimmelzwaan [Pays-Bas] ; Michel Hanss [France] ; Emmanuel Albina [France] ; Marie-Laure Foucault-Grunenwald [France] ; Vuong B. Le [France] ; Stella E. Vogelzang-Van Trierum [Pays-Bas] ; Patrica Gil [France] ; Eric Camerer [France] ; Dominique Martinez [France] ; Bruno Lina [France] ; Roger Lijnen [Belgique] ; Peter Carmeliet [Belgique] ; Beatrice Riteau [France]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2013.
Abstract
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.
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DOI: 10.1371/journal.ppat.1003229
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TA A-15 / G - 34398 Montpellier Cedex 5 ou Domaine Duclos - Prise-D'eau - 97170 Petit-Bourg Guadeloupe ou CRVOI - BP 80005 - 2 rue Maxime Rivière - 97491 Sainte-Clotilde Cedex Réunion ou ISRA/LNERV - Route du Front de Terre - BP 2057 - Dakar Hann Sénégal</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation name="UMR1309" active="#struct-92114" type="direct"></relation> <relation name="UMR15" active="#struct-11574" type="direct"></relation> </listRelation> <tutelles><tutelle name="UMR1309" active="#struct-92114" type="direct"><org type="institution" xml:id="struct-92114" status="OLD"> <orgName>Institut National de la Recherche Agronomique</orgName> <orgName type="acronym">INRA</orgName> <date type="start">1946-05-18</date> <date type="end">2019-12-31</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.inra.fr</ref> </desc> </org></tutelle><tutelle name="UMR15" active="#struct-11574" type="direct"><org type="institution" xml:id="struct-11574" status="VALID"> <idno type="ISNI">0000 0001 2153 9871 </idno> <orgName>Centre de Coopération Internationale en Recherche Agronomique pour le Développement</orgName> <orgName type="acronym">Cirad</orgName> <date type="start">1984-06-01</date> <desc> <address> <addrLine>Siège 42, rue Scheffer 75116 Paris</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.cirad.fr</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country></affiliation></author><author><name sortKey="Lina, Bruno" sort="Lina, Bruno" uniqKey="Lina B" first="Bruno" last="Lina">Bruno Lina</name><affiliation wicri:level="1"><hal:affiliation type="researchteam" xml:id="struct-543794" status="VALID"> <orgName>Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control</orgName> <orgName type="acronym">Virpath</orgName> <date type="start">2016-01-01</date> <desc> <address> <addrLine>Laboratoire de Virologie et Pathologies humaines – VirPathFaculté de médecine RTH LaennecBâtiment B7-11 rue Guillaume Paradin69372 Lyon cedex 08</addrLine> <country key="FR"></country> </address> <ref type="url">http://ciri.inserm.fr</ref> </desc> <listRelation> <relation active="#struct-222995" type="direct"></relation> <relation active="#struct-6818" type="indirect"></relation> <relation active="#struct-194495" type="indirect"></relation> <relation active="#struct-301088" type="indirect"></relation> <relation name="U1111" active="#struct-303623" type="indirect"></relation> <relation name="UMR5308" active="#struct-441569" type="indirect"></relation> </listRelation> <tutelles><tutelle active="#struct-222995" type="direct"><org type="regrouplaboratory" xml:id="struct-222995" status="VALID"> <idno type="IdRef">17825696X</idno> <idno type="RNSR">201320572J</idno> <orgName>Centre International de Recherche en Infectiologie - UMR</orgName> <orgName type="acronym">CIRI</orgName> <date type="start">2013-01-01</date> <desc> <address> <addrLine>21 avenue Tony Garnier 69365 Lyon Cedex 07</addrLine> <country key="FR"></country> </address> <ref type="url">http://ciri.inserm.fr/</ref> </desc> <listRelation> <relation name="U1111" active="#struct-303623" type="direct"></relation> <relation active="#struct-6818" type="direct"></relation> <relation active="#struct-194495" type="direct"></relation> <relation active="#struct-301088" type="indirect"></relation> <relation name="UMR5308" active="#struct-441569" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-6818" type="indirect"><org type="institution" xml:id="struct-6818" status="VALID"> <idno type="IdRef">149154992</idno> <orgName>École normale supérieure - Lyon</orgName> <orgName type="acronym">ENS Lyon</orgName> <desc> <address> <addrLine>15 parvis René Descartes - BP 7000 - 69342 Lyon Cedex 07</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.ens-lyon.eu/</ref> </desc> </org></tutelle><tutelle active="#struct-194495" type="indirect"><org type="institution" xml:id="struct-194495" status="VALID"> <idno type="IdRef">026402823</idno> <idno type="ISNI">0000000121686185</idno> <orgName>Université Claude Bernard Lyon 1</orgName> <orgName type="acronym">UCBL</orgName> <desc> <address> <addrLine>43, boulevard du 11 novembre 1918, 69622 Villeurbanne cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.univ-lyon1.fr/</ref> </desc> <listRelation> <relation active="#struct-301088" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-301088" type="indirect"><org type="regroupinstitution" xml:id="struct-301088" status="VALID"> <orgName>Université de Lyon</orgName> <desc> <address> <addrLine>92 rue Pasteur - CS 30122, 69361 Lyon Cedex 07</addrLine> <country key="FR"></country> </address> <ref type="url">https://www.universite-lyon.fr/</ref> </desc> </org></tutelle><tutelle name="U1111" active="#struct-303623" type="indirect"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc> </org></tutelle><tutelle name="UMR5308" active="#struct-441569" type="indirect"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno> <idno type="ISNI">0000000122597504</idno> <orgName>Centre National de la Recherche Scientifique</orgName> <orgName type="acronym">CNRS</orgName> <date type="start">1939-10-19</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.cnrs.fr/</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country><placeName><settlement type="city">Lyon</settlement><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region></placeName><orgName type="university">Université Claude Bernard Lyon 1</orgName><orgName type="institution" wicri:auto="newGroup">Université de Lyon</orgName></affiliation></author><author><name sortKey="Lijnen, Roger" sort="Lijnen, Roger" uniqKey="Lijnen R" first="Roger" last="Lijnen">Roger Lijnen</name><affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-92863" status="VALID"> <orgName>Université Catholique de Louvain</orgName> <orgName type="acronym">UCL</orgName> <desc> <address> <addrLine>Place de l'Université 1 - 1348 Louvain-La-Neuve</addrLine> <country key="BE"></country> </address> <ref type="url">http://www.uclouvain.be/</ref> </desc> </hal:affiliation><country>Belgique</country></affiliation></author><author><name sortKey="Carmeliet, Peter" sort="Carmeliet, Peter" uniqKey="Carmeliet P" first="Peter" last="Carmeliet">Peter Carmeliet</name><affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-357456" status="INCOMING"> <orgName>Flanders Institute for Biotechnology</orgName> <desc> <address> <country key="BE"></country> </address> </desc> </hal:affiliation><country>Belgique</country></affiliation></author><author><name sortKey="Riteau, Beatrice" sort="Riteau, Beatrice" uniqKey="Riteau B" first="Beatrice" last="Riteau">Beatrice Riteau</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-133404" status="OLD"> <orgName>Département Santé Animale</orgName> <orgName type="acronym">DEPT SA</orgName> <date type="end">2019-12-31</date> <desc> <address> <addrLine>NOUZILLY</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation active="#struct-92114" type="direct"></relation> </listRelation> <tutelles><tutelle active="#struct-92114" type="direct"><org type="institution" xml:id="struct-92114" status="OLD"> <orgName>Institut National de la Recherche Agronomique</orgName> <orgName type="acronym">INRA</orgName> <date type="start">1946-05-18</date> <date type="end">2019-12-31</date> <desc> <address> <country key="FR"></country> </address> <ref type="url">http://www.inra.fr</ref> </desc> </org></tutelle></tutelles></hal:affiliation><country>France</country></affiliation></author></analytic><idno type="DOI">10.1371/journal.ppat.1003229</idno><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><imprint><date type="datePub">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"> <p>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.</p> </div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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