Furman David, Jojic Vladimir, Sharma Shalini, Shen-Orr Shai S, Angel Cesar J L, Onengut-Gumuscu Suna, Kidd Brian A, Maecker Holden T, Concannon Patrick, Dekker Cornelia L, Thomas Paul G, Davis Mark M
Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Sci Transl Med. 2015 Apr 1;7(281):281ra43. doi: 10.1126/scitranslmed.aaa2293.
Cytomegalovirus (CMV) is a β-herpesvirus 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 status. In contrast, CMV-seropositive young adults exhibited enhanced antibody responses to influenza vaccination, increased CD8(+) T cell sensitivity, and elevated levels of circulating interferon-γ compared to seronegative 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 ubiquity of CMV infection in humans and many other species.
巨细胞病毒（CMV）是一种β疱疹病毒，在全球大多数人身上以潜伏形式存在。在免疫抑制个体中，CMV可重新激活并引发严重的临床并发症，但潜伏状态对健康人的影响仍不清楚。我们采用系统方法来了解血清反应阳性和阴性个体之间的差异，并检测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、免疫细胞表型分析、基因表达、细胞对细胞因子刺激的体外反应以及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状态如何，老年个体对疫苗接种的反应降低，免疫成分总体下调。相比之下，与血清反应阴性个体相比，CMV血清反应阳性的年轻成年人对流感疫苗接种的抗体反应增强、CD8(+) T细胞敏感性增加以及循环干扰素-γ水平升高。对感染鼠巨细胞病毒的幼鼠进行的实验也表明，与未感染动物相比，其对流感病毒攻击具有显著的保护作用，尽管这种作用会随着时间而减弱。这些数据表明，CMV及其鼠类对应物可对年轻健康个体的免疫反应产生有益影响，这可能解释了CMV感染在人类和许多其他物种中普遍存在的原因。
