M cell-depletion blocks oral prion disease pathogenesis.
M cell-depletion blocks oral prion disease pathogenesis.
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许多朊病毒疾病是通过口腔获得的。我们的数据显示，口服暴露后，早期朊病毒在Peyer's斑块的滤泡树突状细胞（FDC）上复制是疾病有效传播到大脑（称为神经入侵）的必要条件。在摄入被污染的食物后，朊病毒要在Peyer's斑块内的FDC上复制，它们必须首先穿过肠道上皮。然而，朊病毒进入Peyer's补丁的机制尚不确定。在覆盖Peyer's斑块的滤泡相关上皮内是微褶细胞（M细胞），这是一种特殊的上皮细胞，专门用于颗粒的胞吞作用。我们发现，在M细胞耗尽后，Peyer's斑块中FDC上的早期朊病毒积累被阻断。此外，在口腔暴露时缺乏M细胞，神经侵袭和疾病发展同样被阻断。这些数据表明M细胞是朊病毒从肠腔摄取到Peyer’s补丁的重要部位。
Many prion diseases are orally acquired. Our data show that after oral exposure, early prion replication upon follicular dendritic cells (FDC) in Peyer's patches is obligatory for the efficient spread of disease to the brain (termed neuroinvasion). For prions to replicate on FDC within Peyer's patches after ingestion of a contaminated meal, they must first cross the gut epithelium. However, the mechanism through which prions are conveyed into Peyer's patches is uncertain. Within the follicle-associated epithelium overlying Peyer's patches are microfold cells (M cells), unique epithelial cells specialized for the transcytosis of particles. We show that following M cell-depletion, early prion accumulation upon FDC in Peyer's patches is blocked. Furthermore, in the absence of M cells at the time of oral exposure, neuroinvasion and disease development are likewise blocked. These data suggest M cells are important sites of prion uptake from the gut lumen into Peyer's patches.
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