Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza.
Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza.
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DOI：
10.1038/s41590-018-0111-5
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发表时间：
2018-06
影响因子：
30.5
通讯作者：
MOSAIC Investigators
中科院分区：
文献类型：
--
作者：
Dunning J;Blankley S;Hoang LT;Cox M;Graham CM;James PL;Bloom CI;Chaussabel D;Banchereau J;Brett SJ;Moffatt MF;O'Garra A;Openshaw PJM;MOSAIC Investigators
转录谱和宿主反应生物标志物越来越多地用于研究疾病的严重程度、亚型和发病机制。我们现在描述全血mRNA的签名，局部和全身免疫介质浓度在131例成人住院与流感，从广泛的临床和研究数据获得的MOSAIC财团。在不需要机械通气支持的病例中，干扰素相关的抗病毒途径的特征在症状的第4天是常见的;在需要机械通气的病例中，甚至在疾病的早期，也可以看到炎症、活化的中性粒细胞和细胞应激/死亡（“细菌”）模式。可识别的细菌共感染对于这种“细菌”特征不是必需的，但可以增强其发展，同时减弱早期的“病毒”特征。我们的研究结果强调了时间和严重程度在解释宿主对急性病毒感染的反应中的重要性，并确定了特定的免疫激活模式，这些模式可能有助于开发针对严重流感的新型诊断和治疗工具。
Transcriptional profiles and host response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole blood mRNA signatures, local and systemic immune mediator concentrations in 131 adults hospitalised with influenza from which extensive clinical and investigational data were obtained by the MOSAIC consortium. Signatures reflecting interferon-related antiviral pathways were common up to day 4 of symptoms in cases not requiring mechanical ventilatory support; in those needing mechanical ventilation an inflammatory, activated neutrophil and cell stress/death (‘bacterial’) pattern was seen, even early in disease. Identifiable bacterial co-infection was not necessary for this ‘bacterial’ signature but could enhance its development, while attenuating the early ‘viral’ signature. Our findings emphasise the importance of timing and severity in the interpretation of host responses to acute viral infection, and identify specific patterns of immune activation that may enable the development of novel diagnostic and therapeutic tools for severe influenza.
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影响因子：
5.4
作者：
Ioannidis, Ioannis;McNally, Beth;Flano, Emilio
通讯作者：
Flano, Emilio
影响因子：
32.4
作者：
Obermoser, Gerlinde;Presnell, Scott;Chaussabel, Damien
通讯作者：
Chaussabel, Damien
DOI：
10.1152/ajplung.00283.2015
发表时间：
2015-11-15
影响因子：
4.9
作者：
Gregory, David J.;Kobzik, Lester
通讯作者：
Kobzik, Lester
DOI：
10.1093/infdis/jit190
发表时间：
2013-08-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Falsey AR;Becker KL;Swinburne AJ;Nylen ES;Formica MA;Hennessey PA;Criddle MM;Peterson DR;Baran A;Walsh EE
通讯作者：
Walsh EE
影响因子：
64.8
作者：
Everitt, Aaron R.;Clare, Simon;Pertel, Thomas;John, Sinu P.;Wash, Rachael S.;Smith, Sarah E.;Chin, Christopher R.;Feeley, Eric M.;Sims, Jennifer S.;Adams, David J.;Wise, Helen M.;Kane, Leanne;Goulding, David;Digard, Paul;Anttila, Verneri;Baillie, J. Kenneth;Walsh, Tim S.;Hume, David A.;Palotie, Aarno;Xue, Yali;Colonna, Vincenza;Tyler-Smith, Chris;Dunning, Jake;Gordon, Stephen B.;Smyth, Rosalind L.;Openshaw, Peter J.;Dougan, Gordon;Brass, Abraham L.;Kellam, Paul
通讯作者：
Kellam, Paul