Author:
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
Abstract
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.
Funder
National Health and Medical Research Council
Subject
Immunology,Immunology and Allergy
Cited by
1 articles.
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