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TLR7 promotes chronic airway disease in RSV-infected mice

Respiratory syncytial virus (RSV) commonly infects the upper respiratory tract (URT) of humans, manifesting with mild cold or flu-like symptoms. However, in infants and the elderly, severe disease of the lower respiratory tract (LRT) often occurs and can develop into chronic airway disease. A better...

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Detalles Bibliográficos
Autores principales: Miles, Mark A., Liong, Stella, Liong, Felicia, Coward-Smith, Madison, Trollope, Gemma S., Oseghale, Osezua, Erlich, Jonathan R., Brooks, Robert D., Logan, Jessica M., Hickey, Shane, Wang, Hao, Bozinovski, Steven, O’Leary, John J., Brooks, Doug A., Selemidis, Stavros
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10545951/
https://www.ncbi.nlm.nih.gov/pubmed/37795093
http://dx.doi.org/10.3389/fimmu.2023.1240552
Descripción
Sumario:Respiratory syncytial virus (RSV) commonly infects the upper respiratory tract (URT) of humans, manifesting with mild cold or flu-like symptoms. However, in infants and the elderly, severe disease of the lower respiratory tract (LRT) often occurs and can develop into chronic airway disease. A better understanding of how an acute RSV infection transitions to a LRT chronic inflammatory disease is critically important to improve patient care and long-term health outcomes. To model acute and chronic phases of the disease, we infected wild-type C57BL/6 and toll-like receptor 7 knockout (TLR7 KO) mice with RSV and temporally assessed nasal, airway and lung inflammation for up to 42 days post-infection. We show that TLR7 reduced viral titers in the URT during acute infection but promoted pronounced pathogenic and chronic airway inflammation and hyperreactivity in the LRT. This study defines a hitherto unappreciated molecular mechanism of lower respiratory pathogenesis to RSV, highlighting the potential of TLR7 modulation to constrain RSV pathology to the URT.