Toll-like receptor 5 agonist flagellin reduces influenza A virus replication independently of type I interferon and interleukin 22 and improves antiviral efficacy of oseltamivir
Identifieur interne : 000030 ( Main/Exploration ); précédent : 000029; suivant : 000031Toll-like receptor 5 agonist flagellin reduces influenza A virus replication independently of type I interferon and interleukin 22 and improves antiviral efficacy of oseltamivir
Auteurs : Anne-France Georgel [France] ; Delphine Cayet [France] ; Andrés Pizzorno [France] ; Manuel Rosa-Calatrava [France] ; Christophe Paget [France] ; Valentin Sencio [France] ; Jean Dubuisson [France] ; François Trottein [France] ; Jean Claude Sirard [France] ; Christophe Carnoy [France]Source :
- Antiviral Research [ 0166-3542 ] ; 2019-04.
English descriptors
Abstract
Influenza infections remain a burden on health care systems despite vaccination programs and marketed antiviral drugs. Immunomodulation through activation of innate sensors could represent innovative approaches to fight the flu. This study evaluated the ability of flagellin, agonist of Toll-like receptor 5 (TLR5), to control the replication of influenza A virus (IAV) in mice. First, we showed that systemic or intranasal administration of flagellin activated transcription of anti-viral genes in lung tissue. Prophylactic and therapeutic flagellin administration resulted in decreased levels of viral RNA and infectious virus in the lungs of H3N2 IAV-infected mice. The effect of the flagellin on viral replication was also observed in Ifnar-/- and Il22-/- IAV-infected mice, suggesting a mechanism independent of type I interferon and interleukin 22 signaling. In addition, a combination therapy associating the neuraminidase inhibitor oseltamivir and flagellin was more effective than standalone treatments in reducing pulmonary viral replication. Thus, this study highlights the therapeutic potential of the flagellin to control the replication of the influenza virus.
Url:
DOI: 10.1016/j.antiviral.2019.05.002
Affiliations:
- France
- Auvergne-Rhône-Alpes, Centre-Val de Loire, Rhône-Alpes, Région Centre
- Lyon, Tours
- Centre Val de Loire Université, Université Claude Bernard Lyon 1, Université de Lyon, Université de Tours
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Le document en format XML
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<orgName>Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204</orgName> <orgName type="acronym">CIIL</orgName> <date type="start">2010-01-01</date> <desc> <address> <addrLine>1 Rue du Professeur Calmette - Lille Cedex - 59019 - BP 245</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.ciil.fr/</ref> </desc> <listRelation> <relation name="UMR8204" active="#struct-300166" type="direct"></relation> <relation active="#struct-301247" type="indirect"></relation> <relation name="U1019" active="#struct-303623" type="direct"></relation> <relation name="UMR9017" active="#struct-374570" type="direct"></relation> <relation name="UMR9017" active="#struct-441569" type="direct"></relation> </listRelation> <tutelles><tutelle name="UMR8204" active="#struct-300166" type="direct"><org type="institution" xml:id="struct-300166" status="VALID"> <orgName>Institut Pasteur de Lille</orgName> <date type="start">1894</date> <desc> <address> <addrLine>1 Rue du Professeur Calmette - Lille Cedex - 59019</addrLine> <country key="FR"></country> </address> <ref type="url">https://www.pasteur-lille.fr/accueil/</ref> </desc> <listRelation> <relation active="#struct-301247" type="direct"></relation> </listRelation> </org></tutelle><tutelle active="#struct-301247" type="indirect"><org type="regroupinstitution" xml:id="struct-301247" status="VALID"> <orgName>Réseau International des Instituts Pasteur</orgName> <orgName type="acronym">RIIP</orgName> <desc> <address> <addrLine>25, rue du Dr Roux 75724 Paris Cedex 15</addrLine> <country key="FR"></country> </address> <ref type="url">https://research.pasteur.fr/ip-network</ref> </desc> </org></tutelle><tutelle name="U1019" active="#struct-303623" type="direct"><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="UMR9017" active="#struct-374570" type="direct"><org type="institution" xml:id="struct-374570" status="VALID"> <idno type="IdRef">223446556</idno> <orgName>Université de Lille</orgName> <date type="start">2018-01-01</date> <desc> <address> <addrLine>Lille</addrLine> <country key="FR"></country> </address> <ref type="url">https://www.univ-lille.fr/</ref> </desc> </org></tutelle><tutelle name="UMR9017" active="#struct-441569" type="direct"><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></affiliation></author></analytic><idno type="DOI">10.1016/j.antiviral.2019.05.002</idno><series><title level="j">Antiviral Research</title><idno type="ISSN">0166-3542</idno><imprint><date type="datePub">2019-04</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>Influenza A virus</term><term>TLR5</term><term>flagellin</term><term>interleukin 22</term><term>type I interferon</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"> <p>Influenza infections remain a burden on health care systems despite vaccination programs and marketed antiviral drugs. Immunomodulation through activation of innate sensors could represent innovative approaches to fight the flu. This study evaluated the ability of flagellin, agonist of Toll-like receptor 5 (TLR5), to control the replication of influenza A virus (IAV) in mice. First, we showed that systemic or intranasal administration of flagellin activated transcription of anti-viral genes in lung tissue. Prophylactic and therapeutic flagellin administration resulted in decreased levels of viral RNA and infectious virus in the lungs of H3N2 IAV-infected mice. The effect of the flagellin on viral replication was also observed in Ifnar-/- and Il22-/- IAV-infected mice, suggesting a mechanism independent of type I interferon and interleukin 22 signaling. In addition, a combination therapy associating the neuraminidase inhibitor oseltamivir and flagellin was more effective than standalone treatments in reducing pulmonary viral replication. Thus, this study highlights the therapeutic potential of the flagellin to control the replication of the influenza virus.</p> </div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Centre-Val de Loire</li><li>Rhône-Alpes</li><li>Région Centre</li></region><settlement><li>Lyon</li><li>Tours</li></settlement><orgName><li>Centre Val de Loire Université</li><li>Université Claude Bernard Lyon 1</li><li>Université de Lyon</li><li>Université de Tours</li></orgName></list><tree><country name="France"><noRegion><name sortKey="Georgel, Anne France" sort="Georgel, Anne France" uniqKey="Georgel A" first="Anne-France" last="Georgel">Anne-France Georgel</name></noRegion><name sortKey="Carnoy, Christophe" sort="Carnoy, Christophe" uniqKey="Carnoy C" first="Christophe" last="Carnoy">Christophe Carnoy</name><name sortKey="Cayet, Delphine" sort="Cayet, Delphine" uniqKey="Cayet D" first="Delphine" last="Cayet">Delphine Cayet</name><name sortKey="Dubuisson, Jean" sort="Dubuisson, Jean" uniqKey="Dubuisson J" first="Jean" last="Dubuisson">Jean Dubuisson</name><name sortKey="Paget, Christophe" sort="Paget, Christophe" uniqKey="Paget C" first="Christophe" last="Paget">Christophe Paget</name><name sortKey="Pizzorno, Andres" sort="Pizzorno, Andres" uniqKey="Pizzorno A" first="Andrés" last="Pizzorno">Andrés Pizzorno</name><name sortKey="Rosa Calatrava, Manuel" sort="Rosa Calatrava, Manuel" uniqKey="Rosa Calatrava M" first="Manuel" last="Rosa-Calatrava">Manuel Rosa-Calatrava</name><name sortKey="Sencio, Valentin" sort="Sencio, Valentin" uniqKey="Sencio V" first="Valentin" last="Sencio">Valentin Sencio</name><name sortKey="Sirard, Jean Claude" sort="Sirard, Jean Claude" uniqKey="Sirard J" first="Jean Claude" last="Sirard">Jean Claude Sirard</name><name sortKey="Trottein, Francois" sort="Trottein, Francois" uniqKey="Trottein F" first="François" last="Trottein">François Trottein</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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