Chronic Immune Activation in HIV-1 Infection Contributes to Reduced Interferon Alpha Production via Enhanced CD40:CD40 Ligand Interaction
Chronic Immune Activation in HIV-1 Infection Contributes to Reduced Interferon Alpha Production via Enhanced CD40:CD40 Ligand Interaction
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DOI：
10.1371/journal.pone.0033925
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发表时间：
2012-03-21
期刊：
影响因子：
3.7
通讯作者：
Schmidt, Barbara
中科院分区：
文献类型：
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作者：
Donhauser, Norbert;Pritschet, Kathrin;Schmidt, Barbara
虽然在HIV-1感染中观察到干扰素(干扰素)α产生增加的特征，但循环中的浆细胞样树突状细胞(PDC)对Toll样受体配体刺激的反应受到严重损害。我们在HIV-1感染者身上观察到的这种功能性PDC缺陷，其CD4+T细胞/亩L低于500%，目前还不清楚。我们提供的证据表明，在HIV-1感染中，外周干扰素-α的产生受到肿瘤坏死因子家族成员CD40配体(CD40L)及其受体CD40的增强相互作用的积极抑制，两者都在免疫激活时上调。未经治疗的HIV-1感染者(n=52)的血浆可溶性CD40L水平显著高于长期抗逆转录病毒治疗的患者(n=62，p
Although a signature of increased interferon (IFN-)alpha production is observed in HIV-1 infection, the response of circulating plasmacytoid dendritic cells (PDC) to Toll-like receptor ligand stimulation is substantially impaired. This functional PDC deficit, which we specifically observed in HIV-1 infected individuals with less than 500 CD4+ T cells/mu l, is not well understood. We provide evidence that the peripheral IFN-alpha production in HIV-1 infection is actively suppressed by the enhanced interaction of CD40 ligand (CD40L), a member of the tumor necrosis factor family, and its receptor CD40, which are both upregulated upon immune activation. Plasma levels of soluble CD40L were significantly higher in untreated HIV-1 infected individuals (n = 52) than in subjects on long-term antiretroviral therapy (n = 62, p