Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells
Human immunodeficiency virus type 1 activates plasmacytoid dendritic cells and concomitantly induces the bystander maturation of myeloid dendritic cells
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DOI：
10.1128/jvi.78.10.5223-5232.2004
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发表时间：
2004-05-01
影响因子：
5.4
通讯作者：
Bhardwaj, N
中科院分区：
文献类型：
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作者：
Fonteneau, JF;Larsson, M;Bhardwaj, N
在这项研究中，我们分析了血浆细胞样树突状细胞(PDC)与人类免疫缺陷病毒1型(HIV-1)相互作用的表型和生理后果。PDC是HIV-1的一个细胞靶点，通过产生α/β干扰素(干扰素-α/β)和趋化因子来响应病毒。这种相互作用的结果，特别是对旁观者髓系树突状细胞(CD11c(+)DC)功能的影响，目前尚不清楚。因此，我们评估了HIV-1暴露在不同条件下对这两个DC亚群的影响。体外分离纯化的pDC和CD11c(+)DC与HIV-1共同作用，分析成熟标志、细胞因子的产生、迁移能力和CD4T细胞刺激能力。与接触Toll样受体-7和-8的合成激动剂R-848类似，接触不同感染性甚至化学灭活的非复制型HIV-1毒株的PDDC强烈上调成熟标志如CD83和功能性CCR7的表达。此外，HIV-1激活的pDC产生细胞因子(干扰素-α和肿瘤坏死因子α)，在CCL19的反应下迁移，在共同培养中，成熟的CD11c(+)树突状细胞不被HIV直接激活。PDC也获得了刺激原始的CD4(+)T细胞的能力，尽管效率低于CD11c(+)DC。HIV-1诱导的这两个DC亚群的成熟可能解释了它们从高病毒载量患者的血液中消失的原因，并可能对HIV-1的细胞传播和HIV-1特异性T细胞反应产生重要影响。
In this study, we analyzed the phenotypic and physiological consequences of the interaction of plasmacytoid dendritic cells (pDCs) with human immunodeficiency virus type 1 (HIV-1). pDCs are one cellular target of HIV-1 and respond to the virus by producing alpha/beta interferon (IFN-alpha/beta) and chemokines. The outcome of this interaction, notably on the function of bystander myeloid DC (CD11c(+) DCs), remains unclear. We therefore evaluated the effects of HIV-1 exposure on these two DC subsets under various conditions. Blood-purified pDCs and CD11c(+) DCs were exposed in vitro to HIV-1, after which maturation markers, cytokine production, migratory capacity, and CD4 T-cell stimulatory capacity were analyzed. pDCs exposed to different strains of infectious or even chemically inactivated, nonreplicating HIV-1 strongly upregulated the expression of maturation markers, such as CD83 and functional CCR7, analogous to exposure to R-848, a synthetic agonist of toll-like receptor-7 and -8. In addition, HIV-1-activated pDCs produced cytokines (IFN-alpha and tumor necrosis factor alpha), migrated in response to CCL19 and, in coculture, matured CD11c(+) DCs, which are not directly activated by HIV. pDCs also acquired the ability to stimulate naive CD4(+) T cells, albeit less efficiently than CD11c(+) DCs. This HIV-1-induced maturation of both DC subsets may explain their disappearance from the blood of patients with high viral loads and may have important consequences on HIV-1 cellular transmission and HIV-1-specific T-cell responses.