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 TITLE=TLR7 promotes chronic airway disease in RSV-infected mice JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1240552 DOI=10.3389/fimmu.2023.1240552 ISSN=1664-3224 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.