Role of the GALT in scrapie agent neuroinvasion from the intestine
Role of the GALT in scrapie agent neuroinvasion from the intestine
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DOI：
10.4049/jimmunol.178.6.3757
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发表时间：
2007-03-15
影响因子：
4.4
通讯作者：
Mabbott, Neil A.
中科院分区：
文献类型：
--
作者：
Glaysher, Bridget R.;Mabbott, Neil A.
口服后，一些传染性海绵状脑病(TSE)病原体首先聚集在高尔特中的滤泡树突状细胞(FDCs)上。在小鼠身上的研究表明，这种积累对于将TSE制剂有效地输送到大脑是必需的。然而，哪些Galt在疾病发病机制中起关键作用还不确定。在此使用缺乏特定GALT组分的小鼠来确定它们单独参与从肠道侵入的瘙痒病病原体。在Galts和FDCs(淋巴毒素(LT)α(-/-)小鼠和LTβ(-/-)小鼠)联合缺失的情况下，瘙痒病原体的传播被阻断。当FDC成熟时。在剩余的淋巴组织中诱导，同时缺乏Peyer‘s补丁(PPS)和肠系膜淋巴结的小鼠(野生型(WT)-LTα(-/-)小鼠)或仅缺乏PPS(WT->；LTβ(-/-)小鼠)仍然对疾病耐药，表明PPS发挥着重要作用。虽然早期的瘙痒病原体聚集也发生在肠系膜淋巴结内，但它们在WT->；LT beta(-/-)小鼠中的存在并不能恢复疾病的易感性。我们还表明，分离的淋巴滤泡(ILF)是TSE药物在肠道中聚集的重要新部位。缺乏PPS但含有大量含有FDC的成熟ILF的小鼠死于瘙痒病的时间与对照组小鼠相似。由于ILF的形成和成熟状态是可诱导的，并受肠道菌群的影响，我们的数据表明，这些因素可能显著影响口服TSE药物的易感性。总之，这些数据表明，口服暴露后，TSE制剂在肠道内淋巴组织内的FDCs上积聚对于有效的神经侵袭是至关重要的。
Following oral exposure, some transmissible spongiform encephalopathy (TSE) agents accumulate first upon follicular dendritic cells (FDCs) in the GALT. Studies in mice have shown that this accumulation is obligatory for the efficient delivery of the TSE agent to the brain. However, which GALTs are crucial for disease pathogenesis is uncertain. Mice deficient in specific GALT components were used here to determine their separate involvement in scrapie agent neuroinvasion from the intestine. In the combined absence of the GALTs and FDCs (lymphotoxin (LT)alpha(-/-) mice and LT beta(-/-) mice), scrapie agent transmission was blocked. When FDC maturation. was induced in remaining lymphoid tissues, mice that lacked both Peyer's patches (PPs) and mesenteric lymph nodes (wild-type (WT)-> LT alpha(-/-) mice) or PPs alone (WT -> LT beta(-/-) mice) remained refractory to disease, demonstrating an important role for the PPs. Although early scrapie agent accumulation also occurs within the mesenteric lymph nodes, their presence in WT -> LT beta(-/-) mice did not restore disease susceptibility. We have also shown that isolated lymphoid follicles (ILFs) are important novel sites of TSE agent accumulation in the intestine. Mice that lacked PPs but contained numerous FDC-containing mature ILFs succumbed to scrapie at similar times to control mice. Because the formation and maturation status of ILFs is inducible and influenced by the gut flora, our data suggest that such factors could dramatically affect susceptibility to orally acquired TSE agents. In conclusion, these data demonstrate that following oral exposure TSE agent accumulation upon FDCs within lymphoid tissue within the intestine itself is critically required for efficient neuroinvasion.