Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8018, USA.
Cell Host Microbe. 2009 Nov 19;6(5):446-56. doi: 10.1016/j.chom.2009.09.011.
Morbidity and mortality associated with viral infections increase with age, although the underlying mechanisms are unclear. Here, we investigated whether aging alters inflammatory responses during systemic viral infection and thereby contributes to virus-induced death. We found that infection of aged mice with systemic herpes viruses led to rapid increases in serum IL-17, neutrophil activation, and mortality due to hepatocyte necrosis. In contrast, all young mice survived infection, displaying weaker IL-17 induction and neutrophil activation. Natural killer T (NKT) cells isolated from the livers of aged mice produced more IL-17 than did young cells, and adoptively transferred aged NKT cells induced liver injury in young mice impaired in viral control. Importantly, IL-17 neutralization or neutrophil depletion during viral infection reduced liver damage and prevented death of aged mice. These results demonstrate that, during systemic viral infection, aging alters the host-pathogen interaction to overproduce IL-17, contributing to liver injury and death.
与病毒感染相关的发病率和死亡率随着年龄的增长而增加，尽管其潜在机制尚不清楚。在这里，我们研究了衰老是否会改变系统性病毒感染期间的炎症反应，从而导致病毒诱导的死亡。我们发现，全身性疱疹病毒感染老年小鼠会导致血清白细胞介素-17（IL-17）、中性粒细胞活化迅速增加，并因肝细胞坏死而导致死亡。相比之下，所有年轻小鼠都能在感染中存活，表现出较弱的 IL-17 诱导和中性粒细胞活化。从老年小鼠肝脏中分离出的自然杀伤 T（NKT）细胞比年轻细胞产生更多的白细胞介素-17，并且过继转移的老年 NKT 细胞会在年轻小鼠中诱导肝脏损伤，这些年轻小鼠在病毒控制方面存在缺陷。重要的是，在病毒感染期间中和白细胞介素-17 或耗竭中性粒细胞会减少肝脏损伤并防止老年小鼠死亡。这些结果表明，在系统性病毒感染期间，衰老改变了宿主-病原体相互作用，从而过度产生白细胞介素-17，导致肝脏损伤和死亡。
