Altered Treg and cytokine responses in RSV-infected infants.

Altered Treg and cytokine responses in RSV-infected infants.
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DOI:
10.1038/pr.2016.130
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发表时间:
2016-11
期刊:
影响因子:
3.6
通讯作者:
Varga SM
Varga SM
中科院分区:
医学3区
文献类型:
--
作者:
Christiaansen AF;Syed MA;Ten Eyck PP;Hartwig SM;Durairaj L;Kamath SS;Varga SM

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呼吸道合胞病毒(RSV)是美国一岁以下儿童毛细支气管炎和肺炎的主要原因。宿主免疫应答被认为是RSV诱导的疾病的原因。我们假设婴儿严重RSV感染是由调节性T细胞(Tcells)的宿主免疫应答调节不足介导的,导致免疫病理学。收集了23名1岁以下RSV感染婴儿和17名1岁以下对照婴儿的血液和鼻吸出物。通过流式细胞术从外周血单核细胞测定Treg频率。通过对鼻抽吸物的多重测定来测量24种细胞因子的分析。我们证明,与年龄匹配的对照组相比,RSV感染婴儿的外周血中活化THBE的频率显著降低。令人惊讶的是,包括IL-1β、IL-17 A和IL-23在内的Th 17相关细胞因子与呼吸窘迫临床症状的减轻相关。此外,RSV感染儿童鼻洗液中IL-33蛋白(一种维持粘膜组织Treg稳态的重要细胞因子)的量减少。这些结果表明,Treg数量减少和不能适当控制宿主炎症反应导致严重的RSV感染。
Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in children under one year of age in the United States. The host immune response is believed to contribute to RSV-induced disease. We hypothesize that severe RSV infection in infants is mediated by insufficient regulation of the host immune response of regulatory T cells (Tregs) resulting in immunopathology. Blood and nasal aspirates from 23 RSV-infected and 17 control infants under 1 year of age were collected. Treg frequencies were determined by flow cytometry from peripheral blood mononuclear cells. Analysis of 24 cytokines was measured by multiplex assay on nasal aspirates. We demonstrate that the frequency of activated Tregs is significantly reduced in the peripheral blood of RSV-infected infants compared to age-matched controls. Surprisingly, Th17 related cytokines including IL-1β, IL-17A, and IL-23 were associated with a reduction in clinical symptoms of respiratory distress. In addition, the amount of IL-33 protein in nasal washes, a cytokine important in maintaining Treg homeostasis in mucosal tissues, was decreased in RSV-infected children. These results suggest that decreased Treg numbers and an inability to properly control the host inflammatory response results in severe RSV infection.
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