McCausland Marie R, Juchnowski Steven M, Zidar David A, Kuritzkes Daniel R, Andrade Adriana, Sieg Scott F, Lederman Michael M, Funderburg Nicholas T
Division of Infectious Disease, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
Harrington Heart & Vascular Institute, University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
PLoS One. 2015 Oct 2;10(10):e0139474. doi: 10.1371/journal.pone.0139474. eCollection 2015.
Monocytes are increasingly implicated in the inflammatory consequences of HIV-1 disease, yet their phenotype following antiretroviral therapy (ART) initiation is incompletely defined. Here, we define more completely monocyte phenotype both prior to ART initiation and during 48 weeks of ART.
Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained at baseline (prior to ART initiation) and at weeks 12, 24, and 48 of treatment from 29 patients participating in ACTG clinical trial A5248, an open label study of raltegravir/emtricitibine/tenofovir administration. For comparison, cryopreserved PBMCs were obtained from 15 HIV-1 uninfected donors, each of whom had at least two cardiovascular risk factors. Thawed samples were stained for monocyte subset markers (CD14 and CD16), HLA-DR, CCR2, CX3CR1, CD86, CD83, CD40, CD38, CD36, CD13, and CD163 and examined using flow cytometry.
In untreated HIV-1 infection there were perturbations in monocyte subset phenotypes, chiefly a higher frequency and density (mean fluorescence intensity-MFI) of HLA-DR (%-p = 0.004, MFI-p = .0005) and CD86 (%-p = 0.012, MFI-p = 0.005) expression and lower frequency of CCR2 (p = 0.0002) expression on all monocytes, lower CCR2 density on inflammatory monocytes (p = 0.045) when compared to the expression and density of these markers in controls' monocytes. We also report lower expression of CX3CR1 (p = 0.014) on patrolling monocytes at baseline, compared to levels seen in controls. After ART, these perturbations tended to improve, with decreasing expression and density of HLA-DR and CD86, increasing CCR2 density on inflammatory monocytes, and increasing expression and density of CX3CR1 on patrolling monocytes.
In HIV-1 infected patients, ART appears to attenuate the high levels of activation (HLA-DR, CD86) and to increase expression of the chemokine receptors CCR2 and CX3CR1 on monocyte populations. Circulating monocyte phenotypes are altered in untreated infection and tend to normalize with ART; the role of these cells in the inflammatory environment of HIV-1 infection warrants further study.
单核细胞越来越多地被认为与HIV-1疾病的炎症后果有关，然而抗逆转录病毒治疗（ART）开始后它们的表型尚未完全明确。在此，我们更全面地定义了ART开始前以及ART治疗48周期间的单核细胞表型。
从参与ACTG临床试验A5248（一项关于raltegravir/恩曲他滨/替诺福韦给药的开放标签研究）的29名患者中，在基线（ART开始前）以及治疗的第12、24和48周获取冻存的外周血单核细胞（PBMC）。为作比较，从15名未感染HIV-1的供体中获取冻存的PBMC，每名供体至少有两种心血管危险因素。解冻后的样本用单核细胞亚群标志物（CD14和CD16）、HLA-DR、CCR2、CX3CR1、CD86、CD83、CD40、CD38、CD36、CD13和CD163进行染色，并使用流式细胞术进行检测。
在未经治疗的HIV-1感染中，单核细胞亚群表型存在扰动，主要表现为所有单核细胞上HLA-DR（百分比 - p = 0.004，平均荧光强度 - MFI - p = 0.0005）和CD86（百分比 - p = 0.012，MFI - p = 0.005）表达的频率和密度更高，以及CCR2表达频率更低（p = 0.0002），与对照组单核细胞中这些标志物的表达和密度相比，炎症单核细胞上CCR2密度更低（p = 0.045）。我们还报告，与对照组相比，基线时巡逻单核细胞上CX3CR1的表达更低（p = 0.014）。ART治疗后，这些扰动趋于改善，HLA-DR和CD86的表达和密度降低，炎症单核细胞上CCR2密度增加，巡逻单核细胞上CX3CR1的表达和密度增加。
在HIV-1感染患者中，ART似乎减弱了高水平的激活（HLA-DR、CD86），并增加了单核细胞群体上趋化因子受体CCR2和CX3CR1的表达。未经治疗的感染中循环单核细胞表型发生改变，而ART治疗后趋于正常化；这些细胞在HIV-1感染炎症环境中的作用值得进一步研究。
