TLR5 signaling amplifies airway epithelial cell responses to influenza through a MyD88–JAK1 crosstalk
Year: 2026
Type: preprint
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.
Source: Research Square
Institutions: Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Université de Tours, Infectiologie et santé publique, Plateforme d'Infectiologie Expérimentale, d-fine (Germany), Centre National de la Recherche Scientifique, Inserm, Université Côte d'Azur, Institut de Pharmacologie Moléculaire et Cellulaire, Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, Université de Lille, Institut Pasteur de Lille, Centre Hospitalier Universitaire de Lille, Center for Infection and Immunity of Lille
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7225819761