Increased interferon alpha expression in circulating plasmacytoid dendritic cells of HIV-1-infected patients

Increased interferon alpha expression in circulating plasmacytoid dendritic cells of HIV-1-infected patients
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DOI:
10.1097/qai.0b013e31817f97cf
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发表时间:
2008-08-15
影响因子:
3.6
通讯作者:
Romerio, Fabio
Romerio, Fabio
中科院分区:
医学3区
文献类型:
--
作者:
Lehmann, Clara;Harper, Jill M.;Romerio, Fabio

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背景:浆细胞样树突状细胞(pDC)和干扰素α(IFN α)在HIV-1感染中的作用尚不清楚。一方面,HIV-1疾病与pDC的进行性下降相关,其在体外攻击后显示出产生IFN α的能力降低。另一方面,在HIV-1感染者的高IFN α血清水平已被提出,以促进免疫超活化和疾病progress.Methods:我们试图确定是否消失的pDC在HIV-1疾病是由于归巢在淋巴组织。我们还研究了IFN α和粘病毒抗性蛋白A(MxA)的表达在未刺激的pDC和相关的这些结果与选定的临床和实验室parameters.Results:我们发现,pDC的外周血中显着下降的患者进展到疾病,但在同一时间表达更高水平的IFN α和MxA相比,控制个人。另一方面,我们在HIV-1患者的淋巴结中观察到稳定的pDC计数。循环pDC的频率与CD 4细胞计数直接相关,与病毒载量负相关。然而,我们没有发现IFN α和MxA表达水平,CD 4计数,和viral load.Conclusions之间的相关性:循环pDC急剧下降的过程中的HIV-1疾病,但表达高水平的IFN α,这可能是一个标志性的全身免疫功能障碍。
Background: The role of plasmacytoid dendritic cells (pDC) and interferon alpha (IFN alpha) in HIV-1 infection is still unclear. On one hand, HIV-1 disease is associated with a progressive decline of pDC, which displays reduced ability to produce IFN alpha after in vitro challenge. On the other hand, high IFNa serum levels in HIV-1-infected individuals have been proposed to promote immune hyper-activation and disease progression.Methods: We sought to determine whether disappearance of pDC in HIV-1 disease is due to homing in lymphoid tissues. We also studied IFN alpha and myxovirus resistance protein A (MxA) expression in unstimulated pDC and correlated these results with selected clinical and laboratory parameters.Results: We found that pDC decline markedly in peripheral blood of patients progressing to disease but at the same time express much higher levels of IFN alpha and MxA compared to control individuals. On the other hand, we observed steady pDC counts in lymph nodes of HIV-1 patients. The frequency of circulating pDC correlated directly with CD4 cell counts and inversely with viral load. However, we found no correlation between IFN alpha and MxA expression levels, CD4 counts, and viral load.Conclusions: Circulating pDC decline sharply in the course of HIV-1 disease, but express high levels of IFN alpha, which may represent a hallmark of systemic immune dysfunction.