KLRD1-expressing natural killer cells predict influenza susceptibility.
KLRD1-expressing natural killer cells predict influenza susceptibility.
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DOI：
10.1186/s13073-018-0554-1
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发表时间：
2018-06-14
期刊：
影响因子：
12.3
通讯作者：
Khatri P
中科院分区：
文献类型：
--
作者：
Bongen E;Vallania F;Utz PJ;Khatri P
在美国，每年有数千万人感染流感。除了儿童和老年人等明显的风险群体外，很难预测哪些亚群感染风险更高。病毒攻毒研究，其中健康人类志愿者接种活流感病毒，提供了研究感染易感性的独特机会。预测流感易感性的生物标志物将有助于识别风险群体和设计疫苗。我们应用细胞混合物去卷积来估计来自四项独立流感攻毒研究中全血转录组数据的免疫细胞比例。我们在流感疫苗接种前比较了三个发现队列中有症状的散毒者和无症状的非散毒者血液中的免疫细胞比例，并在一个保留的验证挑战队列中测试了结果。在发现和验证队列中，基线时症状性散毒者的自然杀伤（NK）细胞显著较低。在发现队列中，基线时有症状的散毒者的造血干细胞和祖细胞（HSPC）较高。尽管验证队列中症状性散毒者的HSPC较高，但增加无统计学显著性。我们观察到与NK细胞相关的基因KLRD 1（编码CD 94）在发现和验证队列的基线时在有症状的散毒者中表达水平较低。基线时血液中KLRD 1表达与流感感染症状严重程度呈负相关。鼻病毒攻击研究中鼻上皮感染后8 h的KLRD 1表达也与症状严重程度呈负相关。我们鉴定了表达KLRD 1的NK细胞作为流感易感性的潜在生物标志物。KLRD 1的表达与症状严重程度呈负相关。我们的研究结果支持一种模型，其中表达KLRD 1的NK细胞的早期反应可以控制流感感染。本文的在线版本（10.1186/s13073-018-0554-1）包含补充材料，可供授权用户使用。
Influenza infects tens of millions of people every year in the USA. Other than notable risk groups, such as children and the elderly, it is difficult to predict what subpopulations are at higher risk of infection. Viral challenge studies, where healthy human volunteers are inoculated with live influenza virus, provide a unique opportunity to study infection susceptibility. Biomarkers predicting influenza susceptibility would be useful for identifying risk groups and designing vaccines. We applied cell mixture deconvolution to estimate immune cell proportions from whole blood transcriptome data in four independent influenza challenge studies. We compared immune cell proportions in the blood between symptomatic shedders and asymptomatic nonshedders across three discovery cohorts prior to influenza inoculation and tested results in a held-out validation challenge cohort. Natural killer (NK) cells were significantly lower in symptomatic shedders at baseline in both discovery and validation cohorts. Hematopoietic stem and progenitor cells (HSPCs) were higher in symptomatic shedders at baseline in discovery cohorts. Although the HSPCs were higher in symptomatic shedders in the validation cohort, the increase was statistically nonsignificant. We observed that a gene associated with NK cells, KLRD1, which encodes CD94, was expressed at lower levels in symptomatic shedders at baseline in discovery and validation cohorts. KLRD1 expression in the blood at baseline negatively correlated with influenza infection symptom severity. KLRD1 expression 8 h post-infection in the nasal epithelium from a rhinovirus challenge study also negatively correlated with symptom severity. We identified KLRD1-expressing NK cells as a potential biomarker for influenza susceptibility. Expression of KLRD1 was inversely correlated with symptom severity. Our results support a model where an early response by KLRD1-expressing NK cells may control influenza infection. The online version of this article (10.1186/s13073-018-0554-1) contains supplementary material, which is available to authorized users.
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影响因子：
3
作者：
Liu TY;Burke T;Park LP;Woods CW;Zaas AK;Ginsburg GS;Hero AO
通讯作者：
Hero AO
影响因子：
3.7
作者：
Dou Y;Fu B;Sun R;Li W;Hu W;Tian Z;Wei H
通讯作者：
Wei H
DOI：
10.1093/cid/cis327
发表时间：
2012-07
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Lillie PJ;Berthoud TK;Powell TJ;Lambe T;Mullarkey C;Spencer AJ;Hamill M;Peng Y;Blais ME;Duncan CJ;Sheehy SH;Havelock T;Faust SN;Williams RL;Gilbert A;Oxford J;Dong T;Hill AV;Gilbert SC
通讯作者：
Gilbert SC
影响因子：
7.4
作者：
Muller J;Parizotto E;Antrobus R;Francis J;Bunce C;Stranks A;Nichols M;McClain M;Hill AVS;Ramasamy A;Gilbert SC
通讯作者：
Gilbert SC
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y