Impact of HIV on cell survival and antiviral activity of plasmacytoid dendritic cells.
Impact of HIV on cell survival and antiviral activity of plasmacytoid dendritic cells.
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DOI：
10.1371/journal.pone.0000458
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发表时间：
2007-05-23
期刊：
影响因子：
3.7
通讯作者：
Fauci AS
中科院分区：
文献类型：
--
作者：
Meyers JH;Justement JS;Hallahan CW;Blair ET;Sun YA;O'Shea MA;Roby G;Kottilil S;Moir S;Kovacs CM;Chun TW;Fauci AS
浆细胞样树突状细胞（Plasmacytoid dendritic cells，pDC）是天然免疫的重要介质，主要通过分泌干扰素（interferon，IFN）-α发挥作用。先前的研究已经发现，这些细胞可以在体外抑制HIV;此外，已经显示pDC在HIV感染个体的外周血中严重减少。在本研究中，我们试图确定pDCs直接抑制病毒复制的能力，并描绘潜在的机制，从而pDCs在HIV感染的个体中被耗尽。我们证明激活的pDC通过涉及IFN-α以及其他抗病毒因子的机制强烈抑制自体CD 4 + T细胞中的HIV复制。值得注意的是，来自在没有抗逆转录病毒治疗的情况下维持低水平血浆病毒血症的感染个体的未刺激的pDC能够通过需要细胞-细胞接触的机制离体抑制HIV。我们的数据还表明，凋亡和坏死的pDC的死亡是由HIV与pDC的融合诱导的。总之，我们的数据表明，pDC在控制HIV复制中起重要作用，并且体内高水平的病毒复制与通过凋亡和坏死的pDC细胞死亡相关。阐明pDC抑制体内HIV复制的机制可能对未来的治疗策略具有临床相关意义。
Plasmacytoid dendritic cells (pDCs) are important mediators of innate immunity that act mainly through secretion of interferon (IFN)-α. Previous studies have found that these cells can suppress HIV in vitro; additionally, pDCs have been shown to be severely reduced in the peripheral blood of HIV-infected individuals. In the present study, we sought to determine the ability of pDCs to directly suppress viral replication ex vivo and to delineate the potential mechanisms whereby pDCs are depleted in HIV-infected individuals. We demonstrate that activated pDCs strongly suppress HIV replication in autologous CD4+ T cells via a mechanism involving IFN-α as well as other antiviral factors. Of note, unstimulated pDCs from infected individuals who maintain low levels of plasma viremia without antiretroviral therapy were able to suppress HIV ex vivo via a mechanism requiring cell-to-cell contact. Our data also demonstrate that death of pDCs by both apoptosis and necrosis is induced by fusion of HIV with pDCs. Taken together, our data suggest that pDCs play an important role in the control of HIV replication and that high levels of viral replication in vivo are associated with pDC cell death via apoptosis and necrosis. Elucidation of the mechanism by which pDCs suppress HIV replication in vivo may have clinically relevant implications for future therapeutic strategies.
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DOI：
10.1073/pnas.84.15.5424
发表时间：
1987-08-01
影响因子：
11.1
作者：
MATTHEWS, TJ;WEINHOLD, KJ;BOLOGNESI, DP
通讯作者：
BOLOGNESI, DP
DOI：
10.1073/pnas.95.15.8869
发表时间：
1998-07-21
影响因子：
11.1
作者：
Chun, TW;Engel, D;Fauci, AS
通讯作者：
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影响因子：
15.9
作者：
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通讯作者：
Bhardwaj, N
影响因子：
20.3
作者：
Donaghy, H;Gazzard, B;Patterson, S
通讯作者：
Patterson, S
影响因子：
5.4
作者：
Fonteneau, JF;Larsson, M;Bhardwaj, N
通讯作者：
Bhardwaj, N