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Antiviral Res. 2019 Aug;168:28-35. doi: 10.1016/j.antiviral.2019.05.002. Epub 2019 May 9.

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.

Author information

1
Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France; Groupement des Hôpitaux de l'Institut Catholique de Lille, Lille, France.
2
Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France.
3
Laboratoire Virologie et Pathologie Humaine - VirPath Team, Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.
4
Laboratoire Virologie et Pathologie Humaine - VirPath Team, Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France; VirNext, Faculté de Médecine RTH Laennec, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, 69008, France.
5
Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France; INSERM U1100, Centre d'Etude des Pathologies Respiratoires (CEPR), Université de Tours, France.
6
Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France. Electronic address: jean-claude.sirard@inserm.fr.
7
Univ. Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, Lille, France. Electronic address: christophe.carnoy@univ-lille.fr.

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.

KEYWORDS:

Flagellin; Influenza A virus; Interleukin 22; TLR5; Type I interferon

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