Effect of plasma viremia on apoptosis and immunophenotype of dendritic cells subsets in acute SIVmac239 infection of Chinese rhesus macaques.
Effect of plasma viremia on apoptosis and immunophenotype of dendritic cells subsets in acute SIVmac239 infection of Chinese rhesus macaques.
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DOI：
10.1371/journal.pone.0029036
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Zheng YT
中科院分区：
文献类型：
--
作者：
Xia HJ;Ma JP;Zhang GH;Han JB;Wang JH;Zheng YT
非人灵长类动物如中国恒河猴（ChRhs）为人类传染病研究提供了良好的动物模型。与人类相似，在Ch Rhs的外周血中存在两个主要的树突状细胞（DC）亚群：髓样DC（mDC）和浆细胞样DC（pDC）。在这项研究中，双色荧光激活细胞分选（FACS）分析用于确定主要的DC亚群，即CD 1c + mDC和pDC从Ch Rhs。然后，首次描述了SIVmac 239感染急性期DC亚群的凋亡和免疫表型变化。两种DC亚群均显示CD 4表达降低和CCR 5表达增强;特别是pDC的表达在大多数时间点显著改变。有趣的是，血浆病毒载量与pDCs的CD 4表达呈负相关，而与CCR 5表达呈正相关。在此期间，CD 1c + mDCs和pDCs都通过增强共刺激分子的表达而被激活，同时伴有CCR 7的增加。CD 1c + mDC和pDC表达的CD 80和CD 86与血浆病毒载量呈正相关。我们的分析表明，在SIVmac 239感染的急性期，pDC更容易在感染后凋亡，这可能是由于它们的高表达的CD 4和CCR 5。两种DC亚群均通过上调共刺激分子的表达而激活，有利于控制SIV的复制。然而，仅仅由活化的DC启动的广泛免疫活化可能导致悲剧性的AIDS进展。
Non-human primates such as Chinese rhesus macaques (Ch Rhs) provide good animal models for research on human infectious diseases. Similar to humans, there are two principal subsets of dendritic cells (DCs) in the peripheral blood of Ch Rhs: myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). In this study, two-color fluorescence-activated cell sorting (FACS) analyses were used to identify the main DC subsets, namely CD1c+ mDCs and pDCs from Ch Rhs. Then, the apoptosis and immunophenotype changes of DCs subsets were first described during the acute phase of SIVmac239 infection. Both the DCs subsets showed decreased CD4 expression and enhanced CCR5 expression; in particular, those of pDCs significantly changed at most time points. Interestingly, the plasma viral loads were negatively correlated with CD4 expression, but were positively correlated with CCR5 expression of pDCs. During this period, both CD1c+ mDCs and pDCs were activated by enhancing expressions of co-stimulatory molecules, accompanied with increase in CCR7. Either CD80 or CD86 expressed on CD1c+ mDCs and pDCs was positively correlated with the plasma viral loads. Our analysis demonstrates that the pDCs were more prone to apoptosis after infection during the acute phase of SIVmac239 infection, which may be due to their high expressions of CD4 and CCR5. Both DCs subsets activated through elevating the expression of co-stimulatory molecules, which was beneficial in controlling the replication of SIV. However, a mere broad immune activation initiated by activated DCs may lead to tragic AIDS progression.
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