Key Points Juvenile mice exhibit increased myeloid recruitment during RSV infection. Recruitment and cell matrix factors were noted in juvenile, not adult, mice. These mouse-based data are supported by findings from a human coculture system. Early life respiratory syncytial virus (RSV) infection has been linked to the onset of asthma. Despite this association, our knowledge of the progression of the initial viral infection is limited, and no safe or effective vaccine currently exists. Bronchioalveolar lavage, whole-lung cellular isolation, and gene expression analysis were performed on 3-wk- (juvenile) and 8-wk-old (adult) RSV-infected C57BL/6 mice to investigate age-related differences in immunologic responses; juvenile mice displayed a sustained myeloid infiltrate (including monocytes and neutrophils) with increased RNA expression of Ccl2, Ccl3, and Ccl4, when compared with adult mice, at 72 h postinfection. Juvenile mice demonstrated αSma expression (indicative of myofibroblast activity), increased hyaluronan deposition in the lung parenchyma (attributed to asthma progression), and a lack of CD64 upregulation on the surface of monocytes (which, in conjunction with serum amyloid P, is responsible for clearing residual hyaluronan and cellular debris). RSV infection of human airway epithelial cell, human lung fibroblast, and U937 monocyte cocultures (at air-liquid interface) displayed similar CCL expression and suggested matrix metalloproteinase-7 and MMP9 as possible extracellular matrix modifiers. These mouse data, in conjunction with our findings in human monocytes, suggest that the sustained influx of myeloid cells in the lungs of juvenile mice during acute RSV infection could potentiate extracellular matrix remodeling, facilitating conditions that support the development of asthma.

中文翻译：

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幼年小鼠（而非成年小鼠）在呼吸道合胞病毒感染期间表现出增加的骨髓募集和细胞外基质重塑

要点 幼年小鼠在 RSV 感染期间表现出骨髓募集增加。在幼年小鼠而非成年小鼠中发现了募集和细胞基质因子。这些基于小鼠的数据得到了人类共培养系统的研究结果的支持。生命早期呼吸道合胞病毒 (RSV) 感染与哮喘的发病有关。尽管存在这种关联，但我们对初始病毒感染进展的了解仍然有限，目前还没有安全或有效的疫苗。对 3 周（幼年）和 8 周（成年）RSV 感染的 C57BL/6 小鼠进行支气管肺泡灌洗、全肺细胞分离和基因表达分析，以研究免疫反应中与年龄相关的差异；感染后 72 小时，与成年小鼠相比，幼年小鼠表现出持续的骨髓浸润（包括单核细胞和中性粒细胞），并且 Ccl2、Ccl3 和 Ccl4 的 RNA 表达增加。幼年小鼠表现出 αSma 表达（表明肌成纤维细胞活性）、肺实质中透明质酸沉积增加（归因于哮喘进展）以及单核细胞表面缺乏 CD64 上调（与血清淀粉样蛋白 P 结合，导致清除残留的透明质酸和细胞碎片）。RSV 感染人气道上皮细胞、人肺成纤维细胞和 U937 单核细胞共培养物（在空气-液体界面）显示出相似的 CCL 表达，并表明基质金属蛋白酶 7 和 MMP9 作为可能的细胞外基质修饰剂。这些小鼠数据与我们在人类单核细胞中的研究结果相结合，表明在急性 RSV 感染期间，幼年小鼠肺部的骨髓细胞持续流入可能会增强细胞外基质重塑，从而促进支持哮喘发展的条件。