STAT3-mediated IL-17 production by postseptic T cells exacerbates viral immunopathology of the lung.
STAT3-mediated IL-17 production by postseptic T cells exacerbates viral immunopathology of the lung.
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DOI：
10.1097/shk.0b013e31826f862c
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Carson WF 4th
中科院分区：
文献类型：
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作者：
Mukherjee S;Allen RM;Lukacs NW;Kunkel SL;Carson WF 4th
严重脓毒症的幸存者在继发感染时表现出更高的发病率和死亡率。尽管细菌继发感染已被广泛研究，但有关败血症后病毒感染的数据仍然很少。在严重脓毒症(盲肠结扎和穿孔，CLP)继之呼吸道合胞病毒(RSV)感染的实验性小鼠模型中，与RSV感染的假手术小鼠相比，CLP小鼠的肺部免疫病理加重。呼吸道合胞病毒感染的CLP小鼠肺内粘液产生增加，并与肺内IL-17产生增加有关，证明了这种病毒相关的免疫病理学。与呼吸道合胞病毒感染的假小鼠相比，呼吸道合胞病毒感染的CLP小鼠表现出Th2型细胞因子水平的增加，而肺和淋巴结中干扰素γ的减少。此外，无论外源性细胞因子或封闭抗体的存在如何，CLP小鼠的CD4T细胞在体外都能产生更多的IL-17。这种IL-17产生的增加与CLP小鼠CD4T细胞中STAT3转录因子与IL-17启动子结合的增加有关。此外，在RSV感染之前，体内中和IL-17导致病毒诱导的粘液产生和Th2细胞因子显著减少。综上所述，这些数据提供了证据，表明败血症后的CD4+T细胞通过STAT3介导的基因转录增加而产生IL-17，这可能有助于继发性病毒感染的免疫病理学。
Survivors of severe sepsis exhibit increased morbidity and mortality in response to secondary infections. Although bacterial secondary infections have been widely studied, there remains a paucity of data concerning viral infections post-sepsis. In an experimental mouse model of severe sepsis (cecal ligation and puncture, CLP) followed by respiratory syncytial virus (RSV) infection, exacerbated immunopathology was observed in the lungs of CLP mice compared to RSV-infected sham surgery mice. This virus-associated immunopathology was evidenced by increased mucus production in the lungs of RSV-infected CLP mice and correlated with increased IL-17 production in the lungs. RSV infected CLP mice exhibited increased levels of Th2 cytokines and reduced IFNγ in the lungs and lymph nodes compared to RSV-infected sham mice. In addition, CD4 T cells from CLP mice produced increased IL-17 in vitro irrespective of the presence of exogenous cytokines or blocking antibodies. This increased IL-17 production correlated wth increased STAT3 transcription factor binding to the IL-17 promoter in CD4 T cells from CLP mice. Further, in vivo neutralization of IL-17 prior to RSV infection led to a significant reduction in virus induced mucus production and Th2 cytokines. Taken together, these data provide evidence that post septic CD4+T cells are primed toward IL-17 production via increased STAT3-mediated gene transcription, which may contribute to the immunopathology of a secondary viral infection.