Centre for Respiratory Science and Health, School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia.
Clinical and Health Sciences, University of South Australia, Adelaide, SA, Australia.
Front Immunol. 2023 Sep 14;14:1240552. doi: 10.3389/fimmu.2023.1240552. eCollection 2023.
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.
呼吸道合胞病毒（RSV）通常感染人类的上呼吸道（URT），表现为轻度感冒或流感样症状。然而，在婴儿和老年人中，下呼吸道（LRT）常发生严重疾病，并可发展为慢性气道疾病。更好地了解急性 RSV 感染如何转变为 LRT 慢性炎症性疾病，对于改善患者护理和长期健康结果至关重要。为了模拟疾病的急性和慢性阶段，我们用 RSV 感染野生型 C57BL/6 和 Toll 样受体 7 敲除（TLR7 KO）小鼠，并在感染后长达 42 天的时间内，对鼻、气道和肺部炎症进行了时间性评估。我们发现 TLR7 在急性感染期间降低了 URT 中的病毒滴度，但促进了 LRT 中明显的致病性和慢性气道炎症和高反应性。这项研究定义了 RSV 下呼吸道发病机制的一个迄今为止未被认识的分子机制，突出了 TLR7 调节的潜力，以将 RSV 病理学限制在上呼吸道。
