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.

译文

呼吸道合胞病毒 (RSV) 是一种普遍存在的病毒,优先感染气道上皮细胞,在免疫功能低下的宿主中引起哮喘加重和严重疾病。急性RSV感染会引起肺部炎症。胸腺和激活调节的趋化因子 (TARC) 将Th2细胞募集到炎症部位。我们发现BALB/c小鼠的急性RSV感染增加了肺部的TARC产生。用单个RSV蛋白预防接种BALB/c小鼠可导致RSV感染后肺中Th1或Th2-biased T细胞反应的发展。我们用表达RSV融合 (F) 蛋白或RSV附着 (G) 蛋白的重组痘苗病毒引发动物,分别诱导Th1-和Th2-biased肺记忆T细胞反应。RSV感染后,仅在牛痘病毒G引发的动物中,TARC的产生显着增加。这些数据表明,RSV感染和Th2细胞因子之间的TARC产生存在正反馈环。用IL-4或IL-13培养的RSV感染的肺上皮细胞显示出TARC产生的显着增加。RSV和IL-4/IL-13对TARC产生的协同作用反映了两种刺激 (都在TARC启动子中) 对NF κ B和STAT6的不同诱导。这些发现表明RSV诱导趋化因子TARC,该趋化因子具有将Th2细胞募集到肺的潜力。

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