TLR-4 engagement of dendritic cells confers a BST-2/tetherin-mediated restriction of HIV-1 infection to CD4+ T cells across the virological synapse.
TLR-4 engagement of dendritic cells confers a BST-2/tetherin-mediated restriction of HIV-1 infection to CD4+ T cells across the virological synapse.
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DOI：
10.1186/1742-4690-10-6
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发表时间：
2013-01-11
期刊：
影响因子：
3.3
通讯作者：
Piguet V
中科院分区：
文献类型：
--
作者：
Blanchet FP;Stalder R;Czubala M;Lehmann M;Rio L;Mangeat B;Piguet V
树突状细胞及其亚群位于粘膜表面，是第一批遇到传播病原体的免疫细胞。细胞限制因子BST-2/tetherin(也称为CD317或HM1.24)通过将病毒颗粒保留在许多细胞类型的细胞表面，包括巨噬细胞等原代细胞，有效地限制HIV-1的释放。然而，BST-2/tetherin不能有效地限制未成熟树突状细胞中HIV-1的感染。我们现在报道，干扰素-α治疗和TLR4与脂多糖结合可显著上调髓系(MyDC)和单核细胞来源的树突状细胞(DC)中Bst-2/tetherin的表达。与HeLa或293T细胞相比，未成熟树突状细胞和干扰素-α成熟树突状细胞的感染性HIV-1释放与野生型病毒相比只有轻微的影响。免疫荧光分析表明，在未成熟DC和干扰素-α成熟的DC中，Bst-2/tetherin都被排除在含有Tetraspin富含微域(TEM)的HIV中。相反，在内毒素介导的成熟DC中，BST-2/tetherin对HIV-1感染向CD4+T细胞的转移具有显著的限制作用。此外，脂多糖，而不是干扰素-α刺激未成熟的DC，导致细胞限制因子戏剧性地重新分布到TEMs以及DC和CD4+T细胞之间的病毒学突触。综上所述，我们证明TLR-4在未成熟DC中的参与显著上调了BST-2/tetherin的内在抗病毒活性，在顺式感染跨越DC/T细胞病毒学突触的CD4+T细胞中。控制BST-2/Tetherin等细胞限制因子对HIV-1感染的作用和效力，对设计抗病毒治疗策略具有重要意义。
Dendritic cells and their subsets, located at mucosal surfaces, are among the first immune cells to encounter disseminating pathogens. The cellular restriction factor BST-2/tetherin (also known as CD317 or HM1.24) potently restricts HIV-1 release by retaining viral particles at the cell surface in many cell types, including primary cells such as macrophages. However, BST-2/tetherin does not efficiently restrict HIV-1 infection in immature dendritic cells. We now report that BST-2/tetherin expression in myeloid (myDC) and monocyte-derived dendritic cells (DC) can be significantly up-regulated by IFN-α treatment and TLR-4 engagement with LPS. In contrast to HeLa or 293T cells, infectious HIV-1 release in immature DC and IFN-α–matured DC was only modestly affected in the absence of Vpu compared to wild-type viruses. Strikingly, immunofluorescence analysis revealed that BST-2/tetherin was excluded from HIV containing tetraspanin-enriched microdomains (TEMs) in both immature DC and IFN-α–matured DC. In contrast, in LPS-mediated mature DC, BST-2/tetherin exerted a significant restriction in transfer of HIV-1 infection to CD4+ T cells. Additionally, LPS, but not IFN-α stimulation of immature DC, leads to a dramatic redistribution of cellular restriction factors to the TEM as well as at the virological synapse between DC and CD4+ T cells. In conclusion, we demonstrate that TLR-4 engagement in immature DC significantly up-regulates the intrinsic antiviral activity of BST-2/tetherin, during cis-infection of CD4+ T cells across the DC/T cell virological synapse. Manipulating the function and potency of cellular restriction factors such as BST-2/tetherin to HIV-1 infection, has implications in the design of antiviral therapeutic strategies.
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影响因子：
4.5
作者：
Garcia, E;Pion, M;Piguet, V
通讯作者：
Piguet, V
影响因子：
6.7
作者：
Casartelli N;Sourisseau M;Feldmann J;Guivel-Benhassine F;Mallet A;Marcelin AG;Guatelli J;Schwartz O
通讯作者：
Schwartz O
DOI：
10.1083/jcb.200609050
发表时间：
2007-04-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Deneka M;Pelchen-Matthews A;Byland R;Ruiz-Mateos E;Marsh M
通讯作者：
Marsh M
I型Interferon自分泌 - 核酸环与树突状细胞的Toll样受体诱导的白介素-12p70分泌有关。
影响因子：
15.3
作者：
Gautier, G;Humbert, M;Deauvieau, F;Scuiller, M;Hiscott, J;Bates, EEM;Trinchieri, G;Caux, C;Garrone, P
通讯作者：
Garrone, P
影响因子：
15.9
作者：
de Jong, Marein A. W. P.;de Witte, Lot;Geijtenbeek, Teunis B. H.
通讯作者：
Geijtenbeek, Teunis B. H.