Role of early stress in the individual differences in host response to viral infection
Role of early stress in the individual differences in host response to viral infection
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DOI：
10.1016/j.bbi.2005.09.006
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发表时间：
2006-07-01
影响因子：
15.1
通讯作者：
Sheridan, John F.
中科院分区：
文献类型：
--
作者：
Avitsur, Ronit;Hunzeker, John;Sheridan, John F.
早期的负面生活事件，特别是在新生儿时期，会对健康造成长期、不可逆转的影响。以下研究的目的是检查新生儿应激对流感病毒感染反应的终身影响。在出生后第1-14天，将小鼠幼仔与其母体反复分离（母体分离，MSP）。成年后，这些小鼠感染流感A/PR 8病毒，并测量肺细胞因子和血浆皮质酮对病毒感染的反应。结果表明，MSP增强了对感染的反应的几个方面。首先，感染诱导的肺促炎细胞因子（白细胞介素（IL）-I，IL-6，和肿瘤坏死因子（TNF）-α）的mRNA表达在MSP小鼠相比，控制。此外，MSP增加感染诱导的肺IL-12和干扰素（IFN）-γ，但对IL-18 mRNA没有影响。有趣的是，MSP诱导的IL-1、TNF-α和IFN-7 mRNA表达的增加在雌性中是明显的，但在雄性中不是。这些发现表明，MSP破坏了先天抗性的调节，导致感染性攻击期间肺中细胞因子应答增强。宿主对病毒感染的反应的这些变化伴随着MSP小鼠肺中病毒复制的增加。有趣的是，流感诱导的皮质酮分泌在MSP小鼠中变钝，这表明对病毒的免疫反应性增加是由于缺乏糖皮质激素反馈控制。这些数据表明，新生儿的压力有影响宿主抵抗感染的整个生命。因此，负性生活事件对健康和疾病的长期影响可能是宿主对感染易感性个体差异的基础。(c)2005年爱思唯尔公司All rights reserved.
Early negative life events, especially during the neonatal period, resulted in long lasting, irreversible effects on well being. The goal of the following study was to examine the lifelong effects of neonatal stress on the response to an influenza viral infection. Mouse pups were repeatedly separated from their dams between postnatal days 1-14 (maternal separation, MSP). As adults, these mice were infected with influenza A/PR8 virus and lung cytokine and plasma corticosterone responses to the viral infection were measured. The results indicated that MSP augmented several aspects of the response to infection. First, infection-induced lung proinflammatory cytokine (interleukin (IL)-I, IL-6, and tumor necrosis factor (TNF)-alpha) mRNA expression was higher in MSP mice compared to controls. In addition, MSP augmented infection-induced lung IL-12 and interferon (IFN)-gamma, but had no effect on IL-18 mRNA. Interestingly, MSP-induced increase in IL-1, TNF-alpha and IFN-7 mRNA expression was evident in females, but not in males. These findings suggest that MSP disrupted the regulation of innate resistance resulting in enhanced cytokine responses in the lungs during an infectious challenge. These changes in host response to the viral infection were accompanied by an increase in viral replication in lungs of MSP mice. Interestingly, influenza-induced corticosterone secretion was blunted in MSP mice, suggesting that the increase in immune reactivity to the virus was due to lack of glucocorticoid feedback control. These data demonstrate that neonatal stress has implications for host resistance to infection throughout life. Thus, long lasting effects of negative life events on health and disease may be the basis for the individual differences in host susceptibility to infection. (c) 2005 Elsevier Inc. All rights reserved.