Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants.
Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants.
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DOI：
10.1038/icb.2014.79
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发表时间：
2015-02
影响因子：
4
通讯作者：
Cormier, Stephania A.
中科院分区：
文献类型：
--
作者：
Huang, Huaqiong;Saravia, Jordy;You, Dahui;Shaw, Aaron J.;Cormier, Stephania A.
呼吸道合胞病毒（RSV）感染仍然是一个重大的全球健康负担，不成比例地影响婴儿并导致长期肺部疾病。IL-17 A已被证明参与调节病毒和过敏性肺部炎症反应，这导致最近对其在RSV感染中的作用的兴趣。使用RSV的新生小鼠模型，我们证明与成年小鼠相比，新生小鼠不能产生IL-17 A应答;成年小鼠中主要的直接IL-17 A贡献者是γδ T细胞。在成年小鼠中，IL-17 A的抗体中和引起RSV引起的肺部炎症和气道粘液增加，而对RSV感染的新生儿给予外源性IL-17 A引起炎症减少，但气道粘液没有变化。我们还观察到感染新生儿缺乏促炎细胞因子（IL-1β，IL-6）的产生。使用人脐带血单核细胞（CBMCs）和成人外周血单核细胞（PBMC），我们比较了通过直接视黄酸诱导基因I（RIG-I）激动的炎性小体活化;与PBMC相比，CBMCs未能诱导促炎细胞因子或IL-17 A + γδ T细胞。我们的研究结果表明，RSV疾病的严重程度部分是由新生儿缺乏炎性小体激活和IL-17 A产生介导的。
Respiratory syncytial virus (RSV) infection remains a significant global health burden disproportionately affecting infants and leading to long-term lung disease. IL-17A has been shown to be involved in regulating viral and allergic lung inflammatory responses, which has led to a more recent interest in its role in RSV infection. Using a neonatal mouse model of RSV, we demonstrate that neonates fail to develop IL-17A responses compared to adult mice; the main immediate IL-17A contributor in adults were γδ T cells. Antibody neutralization of IL-17A in adult mice caused increased lung inflammation and airway mucus from RSV, while exogenous IL-17A administration to RSV-infected neonates caused decreased inflammation but no change in airway mucus. We also observed a lack of pro-inflammatory cytokine production (IL-1β, IL-6) from infected neonates. Using human cord blood mononuclear cells (CBMCs) and adult peripheral blood mononuclear cells (PBMCs), we compared inflammasome activation by direct retinoic acid-inducible gene I (RIG-I) agonism; CBMCs failed to induce pro-inflammatory cytokines or IL-17A+ γδ T cells compared to PBMCs. Our results indicate that RSV disease severity is in part mediated by a lack of inflammasome activation and IL-17A production in neonates.
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影响因子：
8
作者：
通讯作者：
--
影响因子：
5.4
作者：
Liu, Ping;Jamaluddin, Mohammad;Brasier, Allan R.
通讯作者：
Brasier, Allan R.
DOI：
10.1056/nejmoa0804877
发表时间：
2009-02-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hall CB;Weinberg GA;Iwane MK;Blumkin AK;Edwards KM;Staat MA;Auinger P;Griffin MR;Poehling KA;Erdman D;Grijalva CG;Zhu Y;Szilagyi P
通讯作者：
Szilagyi P
影响因子：
4.4
作者：
Lalor, Stephen J.;Dungan, Lara S.;Mills, Kingston H. G.
通讯作者：
Mills, Kingston H. G.
影响因子：
5.4
作者：
Cormier, Stephania A.;Shrestha, Bishwas;You, Dahui
通讯作者：
You, Dahui