The Roslin Institute and R(D)SVS, University of Edinburgh, Midlothian, UK.
Immunology. 2014 Sep;143(1):120-9. doi: 10.1111/imm.12294.
Prions are a unique group of pathogens, which are considered to comprise solely of an abnormally folded isoform of the cellular prion protein. The accumulation and replication of prions within secondary lymphoid organs is important for their efficient spread from the periphery to the brain where they ultimately cause neurodegeneration and death. Mononuclear phagocytes (MNP) play key roles in prion disease pathogenesis. Some MNP appear to facilitate the propagation of prions to and within lymphoid tissues, whereas others may aid their clearance by phagocytosis and by destroying them. Our recent data show that an intact splenic marginal zone is important for the efficient delivery of prions into the B-cell follicles where they subsequently replicate upon follicular dendritic cells before infecting the nervous system. Sialoadhesin is an MNP-restricted cell adhesion molecule that binds sialylated glycoproteins. Sialoadhesin is constitutively expressed upon splenic marginal zone metallophilic and lymph node sub-capsular sinus macrophage populations, where it may function to bind sialylated glycoproteins, pathogens and exosomes in the blood and lymph via recognition of terminal sialic acid residues. As the prion glycoprotein is highly sialylated, we tested the hypothesis that sialoadhesin may influence prion disease pathogenesis. We show that after peripheral exposure, prion pathogenesis was unaltered in sialoadhesin-deficient mice; revealing that lymphoid sequestration of prions is not mediated via sialoadhesin. Hence, although an intact marginal zone is important for the efficient uptake and delivery of prions into the B-cell follicles of the spleen, this is not influenced by sialoadhesin expression by the MNP within it.
朊病毒是一组独特的病原体，被认为仅由细胞朊病毒蛋白的异常折叠异构体组成。朊病毒在次级淋巴器官中的积累和复制对于它们从外周有效地传播到大脑至关重要，在那里它们最终导致神经退行性变和死亡。单核吞噬细胞（MNP）在朊病毒病发病机制中发挥关键作用。一些 MNP 似乎促进了朊病毒在淋巴组织中的传播和复制，而另一些 MNP 则通过吞噬作用和破坏它们来帮助清除它们。我们最近的数据表明，完整的脾脏边缘区对于将朊病毒有效地递送到 B 细胞滤泡中至关重要，在那里它们随后在滤泡树突状细胞上复制，然后感染神经系统。唾液酸结合蛋白是一种 MNP 限制性细胞粘附分子，可结合唾液酸化糖蛋白。唾液酸结合蛋白在脾脏边缘区金属亲和性和淋巴结被膜下窦巨噬细胞群中持续表达，在那里它可能通过识别末端唾液酸残基在血液和淋巴中发挥作用，结合唾液酸化糖蛋白、病原体和外泌体。由于朊病毒糖蛋白高度唾液酸化，我们测试了唾液酸结合蛋白可能影响朊病毒病发病机制的假设。我们表明，在周围暴露后，唾液酸结合蛋白缺陷小鼠中的朊病毒发病机制没有改变；揭示了朊病毒在淋巴器官中的隔离不是通过唾液酸结合蛋白介导的。因此，尽管完整的边缘区对于将朊病毒有效地摄取和递送到脾脏的 B 细胞滤泡中很重要，但这不受其中 MNP 表达唾液酸结合蛋白的影响。
