First Department of Internal Medicine.
J Infect Dis. 2014 Mar;209(6):940-9. doi: 10.1093/infdis/jit612. Epub 2013 Nov 19.
Aberrant activation of plasmacytoid dendritic cells (pDCs) with excessive production of interferon alpha (IFNα) represents one of the hallmarks of immune activation during chronic phase of human immunodeficiency virus (HIV) infection. A number of studies have shown that disruption of mucosal integrity in the gut is a cause of persistent immune activation. However, little is known about the role that pDCs play in this process, and our current understanding comes from the simian immunodeficiency virus macaque model. Thus, in the present study we sought to investigate the frequency and function of pDCs in peripheral blood and gut samples from HIV-infected individuals before and 6 months after initiation of antiretroviral therapy (ART). We show that circulating pDCs were depleted in ART-naive HIV+ patients, and upregulated the gut-homing receptor CD103 compared with uninfected controls. By converse, pDCs accumulated in the terminal ileum of ART-naive HIV individuals compared with controls. Baseline levels of IFNα production and markers of immune activation in gut samples of ART-naive HIV subjects were elevated. All these parameters declined after 6 months of ART. Our results suggest that in chronic HIV infection, pDCs migrate from peripheral blood to the gut-associated lymphatic tissue, where they may contribute to immune activation.
浆细胞样树突状细胞（pDCs）的异常激活伴随着干扰素-α（IFNα）的过度产生，这是人类免疫缺陷病毒（HIV）感染慢性期免疫激活的特征之一。许多研究表明，肠道黏膜完整性的破坏是持续免疫激活的原因之一。然而，人们对 pDCs 在这一过程中所起的作用知之甚少，我们目前的认识来自于猴免疫缺陷病毒猕猴模型。因此，在本研究中，我们试图研究接受抗逆转录病毒治疗（ART）前和治疗 6 个月后 HIV 感染者外周血和肠道样本中 pDCs 的频率和功能。结果显示，在未经 ART 治疗的 HIV+患者中，循环 pDCs 被耗尽，与未感染对照相比，上调了归巢受体 CD103。相反，未经 ART 治疗的 HIV 个体的回肠末端积累了 pDCs。未经 ART 治疗的 HIV 受试者肠道样本中 IFNα 产生和免疫激活标志物的基线水平升高。所有这些参数在接受 6 个月的 ART 后均下降。我们的结果表明，在慢性 HIV 感染中，pDCs 从外周血迁移到肠道相关淋巴组织，在那里它们可能有助于免疫激活。
