Immunostimulatory DNA sequences inhibit respiratory syncytial viral load, airway inflammation, and mucus secretion
Immunostimulatory DNA sequences inhibit respiratory syncytial viral load, airway inflammation, and mucus secretion
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DOI：
10.1067/mai.2001.119918
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发表时间：
2001-11-01
影响因子：
14.2
通讯作者：
Broide, DH
中科院分区：
文献类型：
--
作者：
Cho, JY;Miller, M;Broide, DH
目的：研究免疫刺激DNA序列(ISS)能否降低呼吸道合胞病毒(RSV)感染小鼠的病毒载量、黏液分泌、呼吸道炎症和对乙酰甲胆碱的高反应性。方法：在RSV感染前6天给予ISS，观察其对小鼠肺组织RSV病毒载量(病毒滴度和聚合酶链式反应)、支气管肺泡灌洗液细胞因子(干扰素-γ)、呼吸道炎症(支气管周炎症和周期性酸性席夫阳性粘液细胞)、结果：ISS诱导肺组织中抗病毒细胞因子干扰素-γ的表达，并与RSV病毒滴度、黏液分泌和支气管周炎症显著相关。ISS降低了RSV诱导的呼吸道对乙酰胆碱的高反应性，但没有明显抑制。结论：由于ISS诱导了显著水平的肺干扰素-γ，仅基于给予干扰素-γ的免疫策略可能不足以抑制RSV诱导的对乙酰胆碱的气道高反应性，而乙酰胆碱是RSV感染的哮喘患者亚群中重要的终点。
Background: Immunostimulatory DNA sequences (ISS) activate the innate immune system to generate antiviral cytokines, such as IFN-gamma.Objective: This study investigated whether ISS could reduce viral load, mucus secretion, airway inflammation, and airway hyperreactivity to methacholine in a mouse model of respiratory syncytial virus (RSV) infection.Methods: Mice were pretreated with ISS 6 days before RSV infection, and lung indices of RSV viral load (viral titer and PCR), bronchoalveolar lavage fluid cytokines (IFN-gamma), airway inflammation (peribronchial inflammation and periodic acid-Schiff-positive mucus cells), and airway hyperreactivity (methacholine responsiveness) were assessed 4 to 6 days after RSV infection.Results: ISS induced the expression of the antiviral cytokine IFN-gamma in the lung, and this was associated with significantly reduced RSV viral titers, mucus secretion, and peribronchial inflammation. ISS reduced, but did not significantly inhibit, RSV-induced airway hyperreactivity to methacholine.Conclusion: Because ISS induced significant levels of lung IFN-gamma, an immunization strategy based solely on the administration of IFN-gamma may be insufficient to inhibit RSV-induced airway hyperreactivity to methacholine, an endpoint important in the subset of RSV-infected subjects with asthma.