Association of Dynamic Changes in the CD4 T-Cell Transcriptome With Disease Severity During Primary Respiratory Syncytial Virus Infection in Young Infants.
Association of Dynamic Changes in the CD4 T-Cell Transcriptome With Disease Severity During Primary Respiratory Syncytial Virus Infection in Young Infants.
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DOI：
10.1093/infdis/jix400
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发表时间：
2017-11-15
期刊：
影响因子：
--
通讯作者：
Walsh EE
中科院分区：
文献类型：
--
作者：
Mariani TJ;Qiu X;Chu C;Wang L;Thakar J;Holden-Wiltse J;Corbett A;Topham DJ;Falsey AR;Caserta MT;Walsh EE
CD 4 T细胞转录组学结果揭示了与原发性呼吸道合胞病毒感染的疾病严重程度相关的显著变化，有Th 2偏斜的证据，并提供了与疾病严重程度相关的早期T细胞应答的见解。几乎所有儿童在出生后的前2年内都会感染呼吸道合胞病毒（RSV），少数儿童会出现严重疾病（1%-3%住院）。我们假设，使用CD 4 + T淋巴细胞转录组学评估适应性免疫系统，将确定疾病严重程度的基因表达相关性。研究了代表极端临床严重程度的RSV感染婴儿。轻度疾病（n = 23）定义为呼吸频率（RR）< 55且室内空气氧饱和度（SaO 2）≥ 97%，重度疾病（n = 23）定义为RR ≥ 65且SaO 2 ≤ 92%。通过RNA测序评估来自新鲜分选纯化的CD 4 + T细胞的RNA。出生年龄、发病年龄、暴露于环境烟草烟雾、细菌定植和母乳喂养与疾病严重程度相关（校正后P <0.05）。RNA测序分析可靠地测量了大约60%的基因组。RSV疾病的严重程度对CD 4 T细胞基因表达的影响最大。通路分析确定了严重程度的相关性，包括JAK/STAT、催乳素和白细胞介素9信号传导。我们还鉴定了与症状时间和RSV组（A/B）相关的基因和途径。这些数据表明，适应性免疫细胞表型的根本变化可能与RSV临床严重程度相关。
CD4 T-cell transcriptomic results reveal significant changes associated with disease severity in primary respiratory syncytial virus infection, with evidence of Th2 skewing, and provide insight into early T-cell responses associated with disease severity. Nearly all children are infected with respiratory syncytial virus (RSV) within the first 2 years of life, with a minority developing severe disease (1%–3% hospitalized). We hypothesized that an assessment of the adaptive immune system, using CD4+ T-lymphocyte transcriptomics, would identify gene expression correlates of disease severity. Infants infected with RSV representing extremes of clinical severity were studied. Mild illness (n = 23) was defined as a respiratory rate (RR) < 55 and room air oxygen saturation (SaO2) ≥ 97%, and severe illness (n = 23) was defined as RR ≥ 65 and SaO2 ≤ 92%. RNA from fresh, sort-purified CD4+ T cells was assessed by RNA sequencing. Gestational age, age at illness onset, exposure to environmental tobacco smoke, bacterial colonization, and breastfeeding were associated (adjusted P < .05) with disease severity. RNA sequencing analysis reliably measured approximately 60% of the genome. Severity of RSV illness had the greatest effect size upon CD4 T-cell gene expression. Pathway analysis identified correlates of severity, including JAK/STAT, prolactin, and interleukin 9 signaling. We also identified genes and pathways associated with timing of symptoms and RSV group (A/B). These data suggest fundamental changes in adaptive immune cell phenotypes may be associated with RSV clinical severity.
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影响因子：
7.3
作者：
Han JM;Patterson SJ;Levings MK
通讯作者：
Levings MK
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
DOI：
10.1164/rccm.200210-1148oc
发表时间：
2003-09-15
影响因子：
24.7
作者：
Legg, JP;Hussain, IR;Warner, JO
通讯作者：
Warner, JO
影响因子：
2.2
作者：
Misra, Ravi S.;Bhattacharya, Soumyaroop;Mariani, Thomas J.
通讯作者：
Mariani, Thomas J.
T细胞分化，成熟和功能中细胞因子信号传导（SOC）的抑制。
影响因子：
16.8
作者：
Palmer DC;Restifo NP
通讯作者：
Restifo NP