Respiratory syncytial virus synergizes with Th2 cytokines to induce optimal levels of TARC/CCL17
Respiratory syncytial virus synergizes with Th2 cytokines to induce optimal levels of TARC/CCL17
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DOI：
10.4049/jimmunol.179.3.1648
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发表时间：
2007-08-01
影响因子：
4.4
通讯作者：
Hunninghake, Gary W.
中科院分区：
文献类型：
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作者：
Monick, Martha M.;Powers, Linda S.;Hunninghake, Gary W.
呼吸道合胞病毒（RSV）是一种普遍存在的病毒，其优先感染气道上皮细胞，在免疫受损的宿主中引起哮喘恶化和严重疾病。急性RSV感染诱导肺部炎症。Th 2和活化调节趋化因子（TARC）将Th 2细胞募集到炎症部位。我们发现，急性RSV感染的BALB/c小鼠增加TARC的生产在肺。用单个RSV蛋白免疫BALB/c小鼠可导致RSV感染后肺中Th 1或Th 2偏向性T细胞应答的发展。我们用表达RSV融合（F）蛋白或RSV附着（G）蛋白的重组牛痘病毒致敏动物，分别诱导Th 1和Th 2偏向的肺记忆T细胞应答。RSV感染后，TARC的生产显着增加，只有在牛痘病毒G-致敏的动物。这些数据表明RSV感染和Th 2细胞因子之间的TARC产生的正反馈回路。与IL-4或IL-13一起培养的RSV感染的肺上皮细胞表现出TARC产生的显著增加。RSV和IL-4/IL-13对TARC产生的协同作用反映了两种刺激物对NF κ B和STAT 6的不同诱导（两者都在TARC启动子中）。这些发现表明RSV诱导趋化因子TARC，其具有将Th 2细胞募集到肺的潜力。
Respiratory syncytial virus (RSV) is a ubiquitous virus that preferentially infects airway epithelial cells, causing asthma exacerbations and severe disease in immunocompromised hosts. Acute RSV infection induces inflammation in the lung. Thymus- and activation-regulated chemokine (TARC) recruits Th2 cells to sites of inflammation. We found that acute RSV infection of BALB/c mice increased TARC production in the lung. Immunization of BALB/c mice with individual RSV proteins can lead to the development of Th1- or Th2-biased T cell responses in the lung after RSV infection. We primed animals with a recombinant vaccinia virus expressing either the RSV fusion (F) protein or the RSV attachment (G) protein, inducing Th1- and Th2-biased pulmonary memory T cell responses, respectively. After RSV infection, TARC production significantly increased in the vaccinia virus G-primed animals only. These data suggest a positive feedback loop for TARC production between RSV infection and Th2 cytokines. RSV-infected lung epithelial cells cultured with IL-4 or IL-13 demonstrated a marked increase in the production of TARC. The synergistic effect of RSV and IL-4/IL-13 on TARC production reflected differential induction of NF kappa B and STAT6 by the two stimuli (both are in the TARC promoter). These findings demonstrate that RSV induces a chemokine TARC that has the potential to recruit Th2 cells to the lung.