TLR5 signaling amplifies airway epithelial cell responses to influenza through a MyD88–JAK1 crosstalk
Abstract Influenza vaccines and antivirals are compromised by viral evolution, underscoring the need for host-directed strategies that provide broad, strain-independent protection. While flagellin, a Toll-like receptor 5 (TLR5) agonist, has an established role in shielding against respiratory bacterial infection, its role in shaping antiviral defenses in the airway epithelium remains poorly understood. Using porcine bronchial epithelial cells and pigs infected with swine influenza A virus (SIAV), we show that TLR5 activation sensitizes cells to type I interferon (IFN). Flagellin lowered the IFN concentration required for STAT2 activation, amplifying interferon-stimulated gene expression, and suppressing viral replication. This effect required IFN signaling and MyD88, and coincided with a flagellin-induced MyD88–JAK1 interaction. In SIAV-infected pigs, a single administration of flagellin was sufficient to heighten IFN responsiveness and to mitigate disease severity. These findings reveal a novel crosstalk between TLR5 and IFN pathways, offering a strain-independent route to boost antiviral protection.
Authors
- Isabelle Fleurot (ORCID: https://orcid.org/0000-0002-0728-251X)
- Marie Couralet (ORCID: https://orcid.org/0000-0002-4581-8418)
- Gaëlle Simon (ORCID: https://orcid.org/0000-0003-1099-5075)
- Isabelle Seufert (ORCID: https://orcid.org/0000-0001-9811-3836)
- Pascal Barbry (ORCID: https://orcid.org/0000-0001-9632-6483)
- I. V. Parfenova
- Jérémy Pezant
- Emmanuel Kut
- Ferdinand Roesch (ORCID: https://orcid.org/0000-0003-0702-7778)
- Vanaïque Guillory
- Stefanie Ebersberger (ORCID: https://orcid.org/0000-0001-8493-8239)
- Sascha Trapp (ORCID: https://orcid.org/0000-0002-2735-0217)
- Céline Barc (ORCID: https://orcid.org/0000-0002-5912-4652)
- Elaa Chkhaydem
- Laëtitia GAIGEARD (ORCID: https://orcid.org/0009-0001-8327-4132)
- Ignacio Caballero
- jean-claude sirard
Institutions
- Université de Tours (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Côte d'Azur (FR)
- Université de Lille (FR)
- Institut Pasteur de Lille (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Center for Infection and Immunity of Lille (FR)
- d-fine (Germany) (DE)
- Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail (FR)
- Infectiologie et santé publique (FR)
- Institut de Pharmacologie Moléculaire et Cellulaire (FR)
- Plateforme d'Infectiologie Expérimentale (FR)
Publication Details
- Journal
- Research Square
- Published
- 2026-11-11
- DOI
- https://doi.org/10.21203/rs.3.rs-11049330/v1
- Primary Topic
- interferon and immune responses
- Type
- preprint