Cytomegalovirus infection enhances the immune response to influenza.
Cytomegalovirus infection enhances the immune response to influenza.
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DOI：
10.1126/scitranslmed.aaa2293
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发表时间：
2015-04-01
影响因子：
17.1
通讯作者：
Davis MM
中科院分区：
文献类型：
--
作者：
Furman D;Jojic V;Sharma S;Shen-Orr SS;Angel CJ;Onengut-Gumuscu S;Kidd BA;Maecker HT;Concannon P;Dekker CL;Thomas PG;Davis MM
巨细胞病毒（CMV）是一种β-疱疹病毒，以潜伏形式存在于世界各地的大多数人中。在免疫抑制的个体中，CMV可以重新激活并引起严重的临床并发症，但潜伏状态对健康人的影响仍然难以捉摸。我们进行了系统的方法来了解血清阳性和阴性受试者之间的差异，并测量了血液样本中的数百种免疫系统成分，包括细胞因子和趋化因子，免疫细胞表型，基因表达，对细胞因子刺激的体外细胞反应和对季节性流感疫苗接种的抗体反应。正如预期的那样，我们发现无论CMV血清状态如何，老年人对疫苗接种的反应降低，免疫组分整体下调。与此相反，CMV感染的年轻人表现出免疫组分的整体上调，包括对流感疫苗接种的抗体应答增强，CD 8 + T细胞敏感性增加，以及与未感染个体相比循环IFN-γ水平升高。与未感染的动物相比，感染鼠CMV的幼鼠实验也显示出对流感病毒攻击的显著保护，尽管这种效果随着时间的推移而下降。这些数据表明，CMV及其鼠等效物可以对年轻健康个体的免疫应答产生有益的影响，这可以解释CMV和哺乳动物在其进化过程中的持续共存。
Cytomegalovirus (CMV) is a beta-herpes virus present in a latent form in most people worldwide. In immunosuppressed individuals, CMV can reactivate and cause serious clinical complications, but the effect of the latent state on healthy people remains elusive. We undertook a systems approach to understand the differences between seropositive and negative subjects and measured hundreds of immune system components from blood samples including cytokines and chemokines, immune cell phenotyping, gene expression, ex vivo cell responses to cytokine stimuli and the antibody response to seasonal influenza vaccination. As expected, we found decreased responses to vaccination and an overall down-regulation of immune components in aged individuals regardless of CMV serostatus. In contrast, CMV-infected young adults exhibited an overall up-regulation of immune components including enhanced antibody responses to influenza vaccination, increased CD8+ T cell sensitivity, and elevated levels of circulating IFN-γ compared to uninfected individuals. Experiments with young mice infected with murine CMV also showed significant protection from an influenza virus challenge compared with uninfected animals, although this effect declined with time. These data show that CMV and its murine equivalent can have a beneficial effect on the immune response of young, healthy individuals, which may explain the continued coexistence of CMV and mammals throughout their evolution.