Reactive oxygen species delay control of lymphocytic choriomeningitis virus.
Reactive oxygen species delay control of lymphocytic choriomeningitis virus.
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DOI：
10.1038/cdd.2012.167
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发表时间：
2013-04
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
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分化簇（CD）8+ T细胞在慢性病毒感染期间就像一把双刃剑，因为它们不仅促进病毒清除，而且还会诱导病毒介导的免疫病理学。据报道，在病毒感染期间，活性氧（ROS）水平升高。然而，ROS在T细胞介导的免疫病理学中的作用仍不清楚。在这里，我们使用小鼠淋巴细胞性脉络丛脑膜炎病毒，以探讨ROS在病毒清除和诱导免疫病理过程中的作用。我们发现病毒感染导致病毒感染的肝脏和脾脏组织中产生ROS的粒细胞和巨噬细胞水平升高，这些细胞由烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶触发。缺乏NADPH氧化酶的调节亚基p47 phox减少了这些细胞中的ROS产生。虽然CD 8 + T细胞表现出不依赖于NADPH氧化酶表达的ROS产生，但在p47 phox缺陷（Ncf 1 −/−）小鼠中，存活率和T细胞功能升高。在没有p47 phox的情况下，增强的T细胞免疫促进了病毒的清除并钝化了相应的免疫病理学。总之，我们发现NADPH介导的ROS产生严重损害免疫应答，影响病毒的消除和肝细胞损伤的结果。
Cluster of differentiation (CD)8+ T cells are like a double edged sword during chronic viral infections because they not only promote virus elimination but also induce virus-mediated immunopathology. Elevated levels of reactive oxygen species (ROS) have been reported during virus infections. However, the role of ROS in T-cell-mediated immunopathology remains unclear. Here we used the murine lymphocytic choriomeningitis virus to explore the role of ROS during the processes of virus elimination and induction of immunopathology. We found that virus infection led to elevated levels of ROS producing granulocytes and macrophages in virus-infected liver and spleen tissues that were triggered by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Lack of the regulatory subunit p47phox of the NADPH oxidase diminished ROS production in these cells. While CD8+ T cells exhibited ROS production that was independent of NADPH oxidase expression, survival and T-cell function was elevated in p47phox-deficient (Ncf1−/−) mice. In the absence of p47phox, enhanced T-cell immunity promoted virus elimination and blunted corresponding immunopathology. In conclusion, we find that NADPH-mediated production of ROS critically impairs the immune response, impacting elimination of virus and outcome of liver cell damage.
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影响因子：
64.8
作者：
KAGI, D;LEDERMANN, B;HENGARTNER, H
通讯作者：
HENGARTNER, H
影响因子：
5.4
作者：
Boudreau, Howard E.;Emerson, Suzanne U.;Leto, Thomas L.
通讯作者：
Leto, Thomas L.
影响因子：
15.9
作者：
FAUST, LP;ELBENNA, J;CHANOCK, SJ
通讯作者：
CHANOCK, SJ
影响因子：
4.4
作者：
Hultqvist, Malin;Backlund, Johan;Holmdahl, Rikard
通讯作者：
Holmdahl, Rikard
影响因子：
15.9
作者：
Bataller, R;Schwabe, RF;Brenner, DA
通讯作者：
Brenner, DA