In Vivo Depletion of CD11c+ Cells Impairs Scrapie Agent Neuroinvasion from the Intestine1
In Vivo Depletion of CD11c+ Cells Impairs Scrapie Agent Neuroinvasion from the Intestine1
复制标题
体内 CD11c 细胞的耗竭会削弱瘙痒病剂对肠道的神经侵袭1
作者：
Claudine R. Raymond;P. Aucouturier;N. Mabbott
口服暴露后，一些传染性海绵状脑病（TSE）药物首先在GALT的滤泡树突状细胞（dc）上积累。对小鼠的研究表明，TSE剂在GALT，特别是Peyer 's斑块中的积累，是疾病向大脑有效传播的必要条件。然而，TSE药物最初从肠腔传递到GALT的机制尚不清楚。研究表明移动性造血dc参与了这一过程，但缺乏其在体内参与的直接证明。在这项研究中，我们通过使用CD11c-白喉毒素受体转基因小鼠，研究了CD11c+ DCs在瘙痒剂神经侵袭中的作用，CD11c+ DCs可以特异性和短暂地耗尽。使用两种不同的瘙痒剂菌株（ME7和139A瘙痒剂），我们发现当CD11c+ dc在口服暴露前在GALT和脾脏中短暂耗尽时，这些组织中的早期药物积累被阻断。此外，CD11c+细胞缺失降低了对口腔痒病攻击的易感性，表明来自GALT的TSE因子神经侵袭受损。总之，这些数据表明，迁移的CD11c+ dc在瘙痒剂从肠腔转移到GALT中起关键作用，随后发生神经侵袭。
Following oral exposure, some transmissible spongiform encephalopathy (TSE) agents accumulate first upon follicular dendritic cells (DCs) in the GALT. Studies in mice have shown that TSE agent accumulation in the GALT, in particular the Peyer’s patches, is obligatory for the efficient transmission of disease to the brain. However, the mechanism through which TSE agents are initially conveyed from the gut lumen to the GALT is not known. Studies have implicated migratory hemopoietic DCs in this process, but direct demonstration of their involvement in vivo is lacking. In this study, we have investigated the contribution of CD11c+ DCs in scrapie agent neuroinvasion through use of CD11c-diptheria toxin receptor-transgenic mice in which CD11c+ DCs can be specifically and transiently depleted. Using two distinct scrapie agent strains (ME7 and 139A scrapie agents), we show that when CD11c+ DCs were transiently depleted in the GALT and spleen before oral exposure, early agent accumulation in these tissues was blocked. In addition, CD11c+ cell depletion reduced susceptibility to oral scrapie challenge indicating that TSE agent neuroinvasion from the GALT was impaired. In conclusion, these data demonstrate that migratory CD11c+ DCs play a key role in the translocation of the scrapie agent from the gut lumen to the GALT from which neuroinvasion subsequently occurs.
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影响因子：
32.4
作者：
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通讯作者：
Lang, RA
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作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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