Environmental perturbation, inflammation and behavior in healthy and virus-infected mice.
Environmental perturbation, inflammation and behavior in healthy and virus-infected mice.
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健康小鼠和病毒感染小鼠的环境扰动、炎症和行为。
DOI：
10.1016/j.bbi.2013.07.001
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Toth,LindaA
中科院分区：
文献类型：
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作者：
Trammell,RitaA;Verhulst,Steve;Toth,LindaA
所谓的“病态行为”的发展（例如，厌食症、快感缺乏、社会交往减少、疲劳）与免疫反应的各个方面有关。这些问题在慢性潜伏感染期间可能特别麻烦，因为宿主免疫系统必须持续警惕以维持病毒潜伏期。EB病毒（EBV）是一种普遍存在的人类γ-疱疹病毒，可引起急性疾病并在人群中建立终身潜伏期。鼠γ疱疹病毒（MuGHV）是野生啮齿类动物的天然病原体，其为研究小鼠中EBV样γ疱疹病毒的病理生理学提供了实验模型。为了评估该模型在慢性潜伏性病毒疾病期间的疾病行为及其恶化，我们将未感染和MuGHV感染的C57 BL/6 J和BALB/cByJ小鼠暴露于新的和潜在的压力环境扰动，并测量这些挑战对行为和炎症标志物的影响。这些数据表明，小鼠在正常嗜睡期暴露于环境扰动与随后的活动期活动减少有关，尽管中间有休息期。由于感染状态、小鼠品系和暴露于应激环境的独立和交互作用，对炎症介质的影响是复杂的。然而，GCSF和MCP 1在暴露于含有常驻小鼠（DCR）的“脏”笼后立即和12 h在肺中持续升高;这种增加发生在C57 BL/6 J和BALB/cByJ小鼠中，并且与感染状态无关。DCR后12 h，肺组织IL 1 β和IP 10也持续升高。响应于DCR，BALB/cByJ小鼠显示出比C57 BL/6 J小鼠更多的显著细胞因子效应。关于感染状态，无论小鼠品系或DCR暴露如何，在两个时间点肺中的IP 10均一致升高。在一个或两个时间点，血清或肺中的几种分析物受到小鼠品系的影响，E18时血清中存在大多数品系差异。总之，数据显示，小鼠暴露于环境扰动与全身性炎症相关，这部分独立于遗传背景或潜伏性MuGHV感染，并且与可能代表疲劳，抑郁或疾病行为其他方面的活动减少有关。
The development of so-called “sickness behaviors” (e.g., anorexia, anhedonia, reduced social interaction, fatigue) during infectious and inflammatory disease has been linked to facets of the immune response. Such problems can be particularly troublesome during chronic latent infection, as the host immune system must employ continual vigilance to maintain viral latency. Epstein–Barr virus (EBV) is a ubiquitous human gamma-herpesvirus that causes acute disease and establishes life-long latency in people. Murine gammaherpesvirus (MuGHV) is a natural pathogen of wild rodents that provides an experimental model for studying the pathophysiology of an EBV-like gamma-herpesvirus in mice. To evaluate this model with regard to sickness behavior and its exacerbation during a chronic latent viral disease, we exposed uninfected and MuGHV-infected C57BL/6J and BALB/cByJ mice to novel and potentially stressful environmental perturbations and measured the impact of these challenges on behavior and markers of inflammation. The data indicate that exposure of mice to environmental perturbations during the normal somnolent phase is associated with reduced activity during the subsequent active phase, despite an intervening rest period. Effects on inflammatory mediators were complex due to independent and interactive effects of infection status, mouse strain, and exposure to stressful environment. However, GCSF and MCP1 were consistently elevated in lung both immediately after and 12 h after exposure to a “dirty” cage containing the resident mouse (DCR); this increase occurred in both C57BL/6J and BALB/cByJ mice and was independent of infection status. At 12 h after DCR, IL1β and IP10 were also consistently elevated in lung. In response to DCR, BALB/cByJ mice showed a greater number of significant cytokine effects than did C57BL/6J mice. With regard to infection status, IP10 was consistently elevated in lung at both time points regardless of mouse strain or DCR exposure. Several analytes were affected by mouse strain in serum or lung at one or both time points, with most strain differences present in serum at E18. Taken together, the data show that exposure of mice to environmental perturbations is associated with systemic inflammation that is in part independent of genetic background or latent MuGHV infection and with reduced activity that could represent fatigue, depression, or other facets of sickness behavior.