Early accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie
Early accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie
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DOI：
10.1099/0022-1317-81-12-3115
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发表时间：
2000-12-01
影响因子：
3.8
通讯作者：
Lantier, F
中科院分区：
文献类型：
--
作者：
Andréoletti, O;Berthon, P;Lantier, F
已知免疫系统参与瘙痒病发病的早期阶段。然而，自然发生的羊瘙痒病的感染途径及其在宿主中的传播并不完全清楚。在这项研究中，羊瘙痒症的发病机制进行了调查，在绵羊的三个PrP基因型，从2至9个月的年龄，出生和长大在一起，自然羊瘙痒症影响罗曼诺夫岩。通过免疫组织化学方法测定了PrPSc在绵羊器官中积累的动力学。仅在2月龄的敏感VRQ/VRQ绵羊中检测到PrPSc，在回肠派尔集合淋巴结及其引流肠系膜淋巴结处有明显的进入部位。在细胞水平，PrPSc沉积物与圆顶区和B卵泡的CD 68阳性细胞相关，然后在滤泡树突状细胞中检测到。在3至6个月大的羊，PrPSc检测到大多数的肠道相关淋巴组织（GALT），并在较小程度上在更系统的淋巴组织，如脾脏或纵隔淋巴结。所有次级淋巴器官在9个月龄时显示出相似的PrPSc免疫标记强度。在这个时间点，PrPSc还检测到自主肌间神经丛和副交感神经X的脑干核。这些数据表明，自然痒病感染发生的口服途径，通过感染的派尔集合淋巴结，然后在GALT复制。然后，它可能通过支配消化道的自主神经纤维扩散到中枢神经系统。
The immune system is known to be involved in the early phase of scrapie pathogenesis. However, the infection route of naturally occurring scrapie and its spread within the host are not entirely known. In this study, the pathogenesis of scrapie was investigated in sheep of three PrP genotypes, from 2 to 9 months of age, which were born and raised together in a naturally scrapie-affected Romanov Rock. The kinetics of PrPSc accumulation in sheep organs were determined by immunohistochemistry. PrPSc was detected only in susceptible VRQ/VRQ sheep, from 2 months of age, with an apparent entry site at the ileal Peyer's patch as well as its draining mesenteric lymph node. At the cellular level, PrPSc deposits were associated with CD68-positive cells of the dome area and B follicles before being detected in follicular dendritic cells. In 3- to 6-month-old sheep, PrPSc was detected in most of the gut-associated lymphoid tissues (GALT) and to a lesser extent in more systemic lymphoid formations such as the spleen or the mediastinal lymph node. All secondary lymphoid organs showed a similar intensity of PrPSc-immunolabelling at 9 months of age. At this time-point, PrPSc was also detected in the autonomic myenteric nervous plexus and in the nucleus parasympathicus nervi X of the brain stem. These data suggest that natural scrapie infection occurs by the oral route via infection of the Peyer's patches followed by replication in the GALT. It may then spread to the central nervous system through the autonomic nervous fibres innervating the digestive tract.