Prion strain-dependent tropism is maintained between spleen and granuloma and relies on lymphofollicular structures
Prion strain-dependent tropism is maintained between spleen and granuloma and relies on lymphofollicular structures
复制标题
DOI：
10.1038/s41598-019-51084-1
复制
发表时间：
2019-10-10
影响因子：
4.6
通讯作者：
Sibille, Pierre
中科院分区：
文献类型：
--
作者：
Al-Dybiat, Iman;Moudjou, Mohammed;Sibille, Pierre
在外周获得性Pron疾病中，Pron在感染宿主的几个组织中移动，特别是在淋巴组织中，在神经侵袭发生之前很久。积聚甚至可以限制在淋巴组织，而没有神经侵犯和临床疾病。一些实验观察表明，淋巴样结构中分化的滤泡树突状细胞(FDCs)的存在和菌株类型是Pron神经外复制的关键决定因素。在这种背景下，肉芽肿性结构明显缺乏FDCs可以支持Pron复制的报告提出了Pron嗜淋巴的要求的问题。该报告还提出了一种可能性，即非淋巴组织嗜性普恩病毒实际上可以针对这些炎症结构。为了研究这些问题，我们检查了密切相关的普恩病毒的能力，尽管它们具有相反的淋巴趋向性(或FDC依赖性)，但在实验诱导的绵羊PrP转基因小鼠肉芽肿中建立。无论采用何种检测方法，我们都发现在淋巴组织中积聚的Prion容量与肉芽肿之间存在正相关关系。令人惊讶的是，我们还发现肉芽肿内蛋白的聚集涉及与肉芽肿相关的淋巴样结构，并且含有PrP、Mfge-8染色阳性的细胞，而不是强烈提示FDCs的CD45。这些结果表明，FDC对淋巴组织/炎性组织中PrP复制的要求可能与菌株有关。
In peripherally acquired prion diseases, prions move through several tissues of the infected host, notably in the lymphoid tissue, long before the occurrence of neuroinvasion. Accumulation can even be restricted to the lymphoid tissue without neuroinvasion and clinical disease. Several experimental observations indicated that the presence of differentiated follicular dendritic cells (FDCs) in the lymphoid structures and the strain type are critical determinants of prion extraneural replication. In this context, the report that granulomatous structures apparently devoid of FDCs could support prion replication raised the question of the requirements for prion lymphotropism. The report also raised the possibility that nonlymphoid tissue-tropic prions could actually target these inflammatory structures. To investigate these issues, we examined the capacity of closely related prions, albeit with opposite lymphotropism (or FDC dependency), for establishment in experimentally-induced granuloma in ovine PrP transgenic mice. We found a positive correlation between the prion capacity to accumulate in the lymphoid tissue and granuloma, regardless of the prion detection method used. Surprisingly, we also revealed that the accumulation of prions in granulomas involved lymphoid-like structures associated with the granulomas and containing cells that stain positive for PrP, Mfge-8 but not CD45 that strongly suggest FDCs. These results suggest that the FDC requirement for prion replication in lymphoid/inflammatory tissues may be strain-dependent.