The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609 USA.
The Ohio State University, Columbus, OH 43210 USA.
Immun Ageing. 2014 Dec 16;11(1):24. doi: 10.1186/s12979-014-0024-6. eCollection 2014.
Tuberculosis, the disease due to Mycobacterium tuberculosis, is an important cause of morbidity and mortality in the elderly. Use of mouse models may accelerate insight into the disease and tests of therapies since mice age thirty times faster than humans. However, the majority of TB research relies on inbred mouse strains, and these results might not extrapolate well to the genetically diverse human population. We report here the first tests of M. tuberculosis infection in genetically heterogeneous aging mice, testing if old mice benefit from rapamycin.
We find that genetically diverse aging mice are much more susceptible than young mice to M. tuberculosis, as are aging human beings. We also find that rapamycin boosts immune responses during primary infection but fails to increase survival.
Genetically diverse mouse models provide a valuable resource to study how age influences responses and susceptibility to pathogens and to test interventions. Additionally, surrogate markers such as immune measures may not predict whether interventions improve survival.
结核病是由结核分枝杆菌引起的疾病，是老年人发病率和死亡率的重要原因。使用小鼠模型可以加速对该疾病的认识和治疗方法的测试，因为小鼠的衰老速度比人类快三十倍。然而，大多数结核病研究依赖于近交系小鼠品系，这些结果可能不能很好地外推到遗传多样性的人类群体。我们在这里报告了首次在遗传异质的衰老小鼠中进行结核分枝杆菌感染的测试，测试了雷帕霉素是否对老年小鼠有益。
我们发现，遗传异质的衰老小鼠比年轻小鼠更容易感染结核分枝杆菌，衰老的人类也是如此。我们还发现，雷帕霉素在原发性感染期间增强了免疫反应，但未能提高存活率。
遗传异质的小鼠模型为研究年龄如何影响对病原体的反应和易感性以及测试干预措施提供了有价值的资源。此外，免疫等替代标志物可能无法预测干预措施是否能提高存活率。
Zotero 插件
