Department of Allergy and Immunology, National Research Institute for Child Health and Development, Okura, Tokyo, Japan.
Int Arch Allergy Immunol. 2011;154(3):185-94. doi: 10.1159/000321105. Epub 2010 Sep 21.
Respiratory syncytial virus (RSV) infection in infants with Th2 predisposition is thought to increase the risk of allergic sensitization, recurrent wheezing, and bronchial asthma during childhood. We attempted to clarify the molecular mechanisms by which Th1/Th2 predisposition in the host alters RSV infection and facilitates airway inflammation.
A549 human airway epithelial cells were inoculated with live or UV-treated RSV after pretreatment with either a combination of tumor necrosis factor (TNF)-α and interferon-γ (Th1-primed) or a combination of TNF-α and interleukin-4 (Th2-primed) for 48 h. The gene and protein expression profiles of RSV-infected A549 cells were examined.
GeneChip analysis indicated that, at 96 h after inoculation with RSV, the expression of 62 genes was specifically enhanced (more than 2-fold by normalized data) in Th2-primed cells compared to that in unprimed or Th1-primed cells. An increase in mRNA and protein levels of monocyte chemoattractant protein (MCP)-1/CCL2 among those 62 genes was confirmed by real-time PCR and cytometric bead assay, respectively. RSV replication was markedly diminished in Th1-primed airway epithelial cells but not in Th2-primed cells, which was presumably caused at least in part by the early induction of antiviral genes.
These results suggest that Th1/Th2 predisposition in the host prior to RSV infection critically regulates inflammatory reactions in the airways through alteration of gene expression, and that MCP-1/CCL2 plays an important role in the pathogenesis of severe RSV infection and the subsequent development of asthma in Th2-predisposed hosts.
具有 Th2 倾向的婴儿感染呼吸道合胞病毒（RSV）被认为会增加其在儿童期发生过敏致敏、反复喘息和支气管哮喘的风险。我们试图阐明宿主 Th1/Th2 倾向改变 RSV 感染并促进气道炎症的分子机制。
用 TNF-α和 IFN-γ（Th1 预刺激）或 TNF-α和 IL-4（Th2 预刺激）组合预处理后，将活的或 UV 处理的 RSV 接种到 A549 人气道上皮细胞中 48 小时。检查 RSV 感染的 A549 细胞的基因和蛋白质表达谱。
基因芯片分析表明，在接种 RSV 96 小时后，与未刺激或 Th1 预刺激细胞相比，Th2 预刺激细胞中 62 个基因的表达明显增强（通过归一化数据增强 2 倍以上）。通过实时 PCR 和细胞计数珠测定分别证实了其中 62 个基因中单核细胞趋化蛋白-1（MCP-1/CCL2）的 mRNA 和蛋白水平增加。在 Th1 预刺激的气道上皮细胞中，RSV 复制明显减少，但在 Th2 预刺激的细胞中没有，这至少部分是由抗病毒基因的早期诱导引起的。
这些结果表明，宿主在 RSV 感染前的 Th1/Th2 倾向通过改变基因表达，对气道中的炎症反应进行严格调节，MCP-1/CCL2 在严重 RSV 感染和随后在 Th2 倾向宿主中发展为哮喘的发病机制中发挥重要作用。
