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

Anne-France Georgel (1, 2) , Delphine Cayet (2) , Andrés Pizzorno (3) , Manuel Rosa-Calatrava (3) , Christophe Paget (4) , Valentin Sencio (2) , Jean Dubuisson (2) , François Trottein (2) , Jean Claude Sirard (2) , Christophe Carnoy (2)

1 GHICL - Groupement des Hôpitaux de l'Institut Catholique de Lille
2 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
3 Virpath - Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control
4 PRPA - Pathologies Respiratoires : Protéolyse et Aérosolthérapie

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.

Mots clés: flagellin; TLR5; Influenza A virus; type I interferon; interleukin 22

Domaines: Maladies infectieuses

Anne-France Georgel, Delphine Cayet, Andrés Pizzorno, Manuel Rosa-Calatrava, Christophe Paget, et al.. 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. Antiviral Research, 2019, 168, pp.28-35. ⟨10.1016/j.antiviral.2019.05.002⟩. ⟨inserm-02144074⟩