Prion pathogenesis is unaltered following down-regulation of SIGN-R1.
Prion pathogenesis is unaltered following down-regulation of SIGN-R1.
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DOI：
10.1016/j.virol.2016.08.005
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发表时间：
2016-10
期刊：
影响因子：
3.7
通讯作者：
Mabbott, Neil A.
中科院分区：
文献类型：
--
作者：
Bradford, Barry M.;Brown, Karen L.;Mabbott, Neil A.
关键词：
朊病毒疾病是一种传染性神经退行性疾病，其特征是受感染组织中异常朊病毒糖蛋白的积累。外周暴露后，许多朊病毒株在感染大脑之前在淋巴组织的滤泡树突状细胞（FDC）上复制。完整的脾边缘区对于朊病毒向FDC的有效递送至关重要。边缘区包含一个表达特异性细胞间粘附分子-3-抓取非整合素相关1 （SIGN-R1）的巨噬细胞环。这种凝集素结合葡聚糖和荚膜肺炎球菌多糖，并通过与补体成分的相互作用增强对凋亡细胞的清除。由于朊病毒是作为补体调理复合物获得的，我们确定了SIGN-R1在疾病发病机制中的作用。我们发现，在静脉注射朊病毒之前，SIGN-R1的短暂下调对脾FDC中朊病毒的早期积累或随后扩散到大脑没有影响。因此，边缘区巨噬细胞表达SIGN-R1并不限制外周朊病毒疾病的发病机制。朊病毒在感染大脑之前在滤泡树突状细胞上复制。脾边缘区有助于朊病毒向滤泡树突状细胞的传递。边缘区巨噬细胞高度表达SIGN-R1。在SIGN-R1短暂缺失的情况下，研究了朊病毒的发病机制。边缘区巨噬细胞表达SIGN-R1不影响朊病毒的发病机制。
Prion diseases are infectious neurodegenerative disorders characterised by accumulations of abnormal prion glycoprotein in affected tissues. Following peripheral exposure, many prion strains replicate upon follicular dendritic cells (FDC) in lymphoid tissues before infecting the brain. An intact splenic marginal zone is important for the efficient delivery of prions to FDC. The marginal zone contains a ring of specific intercellular adhesion molecule-3-grabbing non-integrin related 1 (SIGN-R1)-expressing macrophages. This lectin binds dextran and capsular pneumococcal polysaccharides, and also enhances the clearance of apoptotic cells via interactions with complement components. Since prions are acquired as complement-opsonized complexes we determined the role of SIGN-R1 in disease pathogenesis. We show that transient down-regulation of SIGN-R1 prior to intravenous prion exposure had no effect on the early accumulation of prions upon splenic FDC or their subsequent spread to the brain. Thus, SIGN-R1 expression by marginal zone macrophages is not rate-limiting for peripheral prion disease pathogenesis. Prions replicate on follicular dendritic cells before infecting the brain. The splenic marginal zone aids the delivery of prions to follicular dendritic cells. Marginal zone macrophages express SIGN-R1 highly. Prion pathogenesis was studies in the transient absence of SIGN-R1 expression. SIGN-R1 expression by marginal zone macrophages does not influence prion pathogenesis.
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影响因子：
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