Girkin Jason L N, Maltby Steven, Bartlett Nathan W
Viral Immunology and Respiratory Disease Group, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.
Priority Research Centre for Healthy Lungs, University of Newcastle and Hunter Medical Research Institute, Newcastle, Australia.
Eur Respir Rev. 2022 May 4;31(164). doi: 10.1183/16000617.0274-2021. Print 2022 Jun 30.
Respiratory virus infections initiate in the upper respiratory tract (URT). Innate immunity is critical for initial control of infection at this site, particularly in the absence of mucosal virus-neutralising antibodies. If the innate immune response is inadequate, infection can spread to the lower respiratory tract (LRT) causing community-acquired pneumonia (as exemplified by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019). Vaccines for respiratory viruses (influenza and SARS-CoV-2) leverage systemic adaptive immunity to protect from severe lung disease. However, the URT remains vulnerable to infection, enabling viral transmission and posing an ongoing risk of severe disease in populations that lack effective adaptive immunity.Innate immunity is triggered by host cell recognition of viral pathogen-associated molecular patterns molecular sensors such as Toll-like receptors (TLRs). Here we review the role of TLRs in respiratory viral infections and the potential of TLR-targeted treatments to enhance airway antiviral immunity to limit progression to severe LRT disease and reduce person-to-person viral transmission. By considering cellular localisation and antiviral mechanisms of action and treatment route/timing, we propose that cell surface TLR agonist therapies are a viable strategy for preventing respiratory viral diseases by providing immediate, durable pan-viral protection within the URT.
呼吸道病毒感染始于上呼吸道（URT）。固有免疫对于在此部位初步控制感染至关重要，尤其是在缺乏黏膜病毒中和抗体的情况下。如果固有免疫反应不足，感染可扩散至下呼吸道（LRT），导致社区获得性肺炎（如严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）/2019冠状病毒病所示）。呼吸道病毒（流感和SARS-CoV-2）疫苗利用全身适应性免疫来预防严重肺部疾病。然而，上呼吸道仍然易受感染，从而导致病毒传播，并在缺乏有效适应性免疫的人群中持续存在严重疾病的风险。固有免疫由宿主细胞对病毒病原体相关分子模式的识别触发，这些分子模式由诸如Toll样受体（TLRs）等分子传感器识别。在此，我们综述了TLRs在呼吸道病毒感染中的作用，以及靶向TLR治疗增强气道抗病毒免疫以限制进展为严重下呼吸道疾病并减少人际病毒传播的潜力。通过考虑细胞定位、抗病毒作用机制以及治疗途径/时间，我们提出细胞表面TLR激动剂疗法是一种可行的策略，可通过在上呼吸道内提供即时、持久的泛病毒保护来预防呼吸道病毒疾病。
