Defaweux Valérie, Dorban Gauthier, Antoine Nadine, Piret Joëlle, Gabriel Annick, Jacqmot Olivier, Falisse-Poirier Nandini, Flandroy Sylvain, Zorzi Danièle, Heinen Ernst
Institute of Human Histology, Department of Morphology and Immunology, Faculty of Medicine, University of Liège, Liège, Belgium.
Cell Tissue Res. 2007 Jul;329(1):35-44. doi: 10.1007/s00441-007-0396-4. Epub 2007 Apr 4.
During preclinical stages of cattle orally infected with bovine spongiform encephalopathy (BSE), the responsible agent is confined to ileal Peyer's patches (IPP), namely in nerve fibers and in lymph follicles, before reaching the peripheral and central nervous systems. No infectivity has been reported in other bovine lymphoid organs, including jejunal Peyer's patches (JPP). To determine the potential sites for prion neuroinvasion in IPP, we analyzed the mucosal innervation and the interface between nerve fibers and follicular dendritic cells (FDC), two dramatic influences on neuroinvasion. Bovine IPP were studied at three ages, viz., newborn calves, calves less than 12 months old, and bovines older than 24 months, and the parameters obtained were compared with those of JPP. No differences in innervation patterns between IPP and JPP were found. The major difference observed was that, in calves of less than 12 months, IPP were the major mucosal-associated lymphoid organ that possessed a large number of follicles with extended FDC networks. Using a panel of antibodies, we showed that PP in 24-month-old bovines were highly innervated at various strategic sites assumed to be involved in the invasion and replication of the BSE pathogen: the suprafollicular dome, T cell area, and germinal centers. In PP in calves of less than 12 months old, no nerve fibers positive for the neurofilament markers NF-L (70 kDa) and NF-H (200 kDa) were observed in contact with FDC. Thus, in view of the proportion of these protein subunits present in neurofilaments, the innervation of the germinal centers can be said to be an age-dependent dynamic process. This variation in innervation might influence the path of neuroinvasion and, thus, the susceptibility of bovines to the BSE agent.
在牛经口感染牛海绵状脑病（BSE）的临床前阶段，致病因子在到达外周和中枢神经系统之前，局限于回肠派伊尔结（IPP），即在神经纤维和淋巴滤泡中。在包括空肠派伊尔结（JPP）在内的其他牛淋巴器官中未报告有传染性。为了确定IPP中朊病毒神经侵袭的潜在部位，我们分析了黏膜神经支配以及神经纤维与滤泡树突状细胞（FDC）之间的界面，这两者对神经侵袭有重大影响。对新生犊牛、12月龄以下犊牛和24月龄以上牛这三个年龄段的牛IPP进行了研究，并将获得的参数与JPP的参数进行比较。未发现IPP和JPP在神经支配模式上有差异。观察到的主要差异是，在12月龄以下的犊牛中，IPP是主要的黏膜相关淋巴器官，拥有大量具有扩展FDC网络的滤泡。使用一组抗体，我们发现24月龄牛的派伊尔结在假定参与BSE病原体侵袭和复制的各个关键部位高度神经支配：滤泡上圆顶、T细胞区和生发中心。在12月龄以下犊牛的派伊尔结中，未观察到与FDC接触的神经丝标志物NF-L（70 kDa）和NF-H（200 kDa）阳性的神经纤维。因此，鉴于这些蛋白质亚基在神经丝中的比例，生发中心的神经支配可说是一个年龄依赖性的动态过程。这种神经支配的变化可能会影响神经侵袭的途径，从而影响牛对BSE病原体的易感性。
