Miles, M.A.Liong, S.Liong, F.Coward Smith, M.Trollope, G.S.Oseghale, O.Erlich, J.R.Brooks, R.D.Logan, J.M.Hickey, S.Wang, H.Bozinovski, S.O'Leary, J.J.Brooks, D.A.Selemidis, S.2025-12-182025-12-182023Frontiers in Immunology, 2023; 14:1-211664-32241664-3224https://hdl.handle.net/11541.2/36160Data source: Supplementary material, https://doi.org/10.3389/fimmu.2023.1240552Respiratory 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.enCopyright 2023 Miles, Liong, Liong, Coward-Smith, Trollope, Oseghale, Erlich, Brooks, Logan, Hickey, Wang, Bozinovski, O’Leary, Brooks and Selemidis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. (https://creativecommons.org/licenses/by/4.0/)toll-like receptor 7respiratory syncytial virusinflammationairway hyperreactivityviral infectionBronchiAnimalsMice, Inbred C57BLMice, KnockoutMiceRespiratory Syncytial Virus InfectionsAsthmaPulmonary Disease, Chronic ObstructiveJournal article10.3389/fimmu.2023.1240552001072785900001Hickey, S. [0000-0002-3063-531X]Brooks, D.A. [0000-0001-9098-3626]