Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, New Lambton Heights, Newcastle, New South Wales, Australia.
Department of Immunology, Juntendo University School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan.
Mucosal Immunol. 2014 May;7(3):478-88. doi: 10.1038/mi.2013.65. Epub 2013 Sep 18.
Respiratory infections in early life can lead to chronic respiratory disease. Chlamydia infections are common causes of respiratory disease, particularly pneumonia in neonates, and are linked to permanent reductions in pulmonary function and the induction of asthma. However, the immune responses that protect against early-life infection and the mechanisms that lead to chronic lung disease are incompletely understood. Here we identify novel roles for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in promoting Chlamydia respiratory infection-induced pathology in early life, and subsequent chronic lung disease. By infecting TRAIL-deficient neonatal mice and using neutralizing antibodies against this factor and its receptors in wild-type mice, we demonstrate that TRAIL is critical in promoting infection-induced histopathology, inflammation, and mucus hypersecretion, as well as subsequent alveolar enlargement and impaired lung function. This suggests that therapeutic agents that target TRAIL or its receptors may be effective treatments for early-life respiratory infections and associated chronic lung disease.
生命早期的呼吸道感染可导致慢性呼吸道疾病。衣原体感染是呼吸道疾病的常见病因，尤其是新生儿肺炎，与肺功能永久性下降和哮喘的发生有关。然而，对抗生命早期感染的免疫反应以及导致慢性肺病的机制尚不完全清楚。在这里，我们确定了肿瘤坏死因子相关凋亡诱导配体（TRAIL）在促进生命早期衣原体呼吸道感染诱导的病理和随后的慢性肺病中的新作用。通过感染 TRAIL 缺陷型新生小鼠，并在野生型小鼠中使用针对该因子及其受体的中和抗体，我们证明 TRAIL 对于促进感染诱导的组织病理学、炎症和黏液分泌过度以及随后的肺泡扩大和肺功能受损至关重要。这表明靶向 TRAIL 或其受体的治疗药物可能是治疗生命早期呼吸道感染和相关慢性肺病的有效方法。
