Chronic lymphocytic inflammation specifies the organ tropism of prions
Chronic lymphocytic inflammation specifies the organ tropism of prions
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DOI：
10.1126/science.1106460
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发表时间：
2005-02-18
期刊：
影响因子：
56.9
通讯作者：
Aguzzi, A
中科院分区：
文献类型：
--
作者：
Heikenwalder, M;Zeller, N;Aguzzi, A
朊病毒通常积聚在神经和淋巴组织中。由于淋巴朊病毒复制需要促炎细胞因子和免疫细胞，我们测试了炎症条件是否影响朊病毒的发病机制。我们给患有肾脏、胰腺或肝脏五种炎症性疾病的小鼠注射朊病毒。在所有情况下，慢性淋巴细胞炎症都会使朊病毒在原本无朊病毒的器官中积聚。炎症灶始终与表达正常细胞朊病毒蛋白PrPc的FDC-M1（+）细胞的光敏素上调和异位诱导相关。相比之下，缺乏PrPsc-α或其受体的小鼠的发炎器官不会积累异常的同种型PrPsc，也不会在朊病毒接种后显示感染性。通过扩大朊病毒的组织分布，慢性炎症性疾病可作为自然和医源性朊病毒传播的调节剂。
Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with five inflammatory diseases of the kidney, pancreas, or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin up-regulation and ectopic induction of FDC-M1(+) cells expressing the normal cellular prion protein PrPc. By contrast, inflamed organs of mice lacking lymphotoxin-alpha or its receptor did not accumulate the abnormal isoform PrPsc, nor did they display infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.