Pertussis toxin sensitization alters the pathogenesis of subsequent respiratory syncytial virus infection
Pertussis toxin sensitization alters the pathogenesis of subsequent respiratory syncytial virus infection
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DOI：
10.1086/315806
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发表时间：
2000-10-01
影响因子：
6.4
通讯作者：
Graham, BS
中科院分区：
文献类型：
--
作者：
Fischer, JE;Johnson, JE;Graham, BS
有证据表明，宿主和病毒因素都影响呼吸道合胞病毒（RSV）感染后的疾病严重程度。为了表征百日咳毒素（PT）致敏对随后RSV感染的影响，在RSV攻击前，BALB/c小鼠经肠外注射PT。在RSV攻击前用纯化和解毒的PT启动，增加了攻击后的体重减轻和死亡率。PT启动改变了肺细胞浸润的动力学、位置和组成，但既没有改变抗体反应，也没有改变病毒滴度，PT致敏的脾细胞的被动转移产生了类似的反应。用纯化的，但不是遗传解毒的，PT对RSV抗原有适度的2型细胞因子反应。然而，在RSV攻击前抗白细胞介素-4治疗未能消除PT启动的作用，这些数据证实了预先存在的免疫环境可以改变病毒特异性免疫，并为RSV疾病的研究提供了模型和非感染性免疫调节剂可能影响病原体特异性免疫的证据。
Evidence suggests that both host and viral factors influence disease severity after infection with respiratory syncytial virus (RSV), To characterize the effects of pertussis toxin (PT) sensitization on subsequent RSV infection, BALB/c mice were treated with PT parenterally before RSV challenge. Priming with purified and detoxified PT before RSV challenge increased postchallenge weight loss and mortality. PT priming changed the kinetics, location, and composition of the cellular infiltrate in the lung but altered neither antibody responses nor virus titers, Passive transfer of PT-sensitized splenocytes produced similar responses. Priming with purified, but not genetically detoxified, PT propagated a modest type 2 cytokine response to RSV antigens. However, anti-interleukin-4 treatment before RSV challenge failed to abrogate the effects of PT priming, These data confirm that the preexisting immune environment can change virus-specific immunity and provide both a model for study of RSV disease and evidence that noninfectious immunomodulators may impact pathogen-specific immunity.