Blood Myeloid Dendritic Cells from HIV-1-Infected Individuals Display a Proapoptotic Profile Characterized by Decreased Bcl-2 Levels and by Caspase-3+ Frequencies That Are Associated with Levels of Plasma Viremia and T Cell Activation in an Exploratory Study
Blood Myeloid Dendritic Cells from HIV-1-Infected Individuals Display a Proapoptotic Profile Characterized by Decreased Bcl-2 Levels and by Caspase-3+ Frequencies That Are Associated with Levels of Plasma Viremia and T Cell Activation in an Exploratory Study
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DOI：
10.1128/jvi.01118-10
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发表时间：
2011-01-01
影响因子：
5.4
通讯作者：
Wilson, Cara C.
中科院分区：
文献类型：
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作者：
Dillon, Stephanie M.;Friedlander, Laura J.;Wilson, Cara C.
在整个疾病过程中，在hiv -1感染者的外周血中观察到髓细胞和浆细胞样树突状细胞（DC）亚群（分别为mDCs和pDCs）的频率降低。淋巴结中DC的积累可能是血液中DC数量减少的部分原因，但DC死亡率的增加也可能是一个促成因素。我们使用多参数流式细胞术来评估未经治疗的hiv -1感染供者、接受抗逆转录病毒治疗（ART）之前和之后的一部分感染供者以及未感染对照供者的血液mDCs和pDCs中的促凋亡和抗凋亡标志物。来自未经治疗的hiv -1感染供者的血液mDCs（而非pDCs）表达的抗凋亡Bcl-2水平低于来自未感染供者的dc。一部分hiv -1感染的供者出现促凋亡性caspase-3（+）血液mDC的频率升高，并且观察到caspase-3(+) mDC的频率与血浆病毒载量和CD8(+) t细胞激活水平呈正相关。Caspase-3(+) mDC频率，而不是mDC Bcl-2表达，随着ART的病毒抑制而降低。我们还对一组未经治疗、感染hiv -1的慢性疾病供者的血液和LN样本中dc上的细胞凋亡标志物进行了评估。LN mDCs比匹配的血液mDCs表现出更高的Bcl-2水平和更低的caspase-3（+）频率。相反，LN pDCs表达的Bcl-2水平低于其血液对应体。总之，未经治疗的HIV-1感染受试者的血液mdc显示出促凋亡特征，这在一定程度上被病毒抑制逆转，这表明在慢性、未经治疗的HIV疾病中，DC死亡可能是导致血液DC耗竭的一个因素。
Reduced frequencies of myeloid and plasmacytoid dendritic cell (DC) subsets (mDCs and pDCs, respectively) have been observed in the peripheral blood of HIV-1-infected individuals throughout the course of disease. Accumulation of DCs in lymph nodes (LNs) may partly account for the decreased numbers observed in blood, but increased DC death may also be a contributing factor. We used multiparameter flow cytometry to evaluate pro- and antiapoptotic markers in blood mDCs and pDCs from untreated HIV-1-infected donors, from a subset of infected donors before and after receiving antiretroviral therapy (ART), and from uninfected control donors. Blood mDCs, but not pDCs, from untreated HIV-1-infected donors expressed lower levels of antiapoptotic Bcl-2 than DCs from uninfected donors. A subset of HIV-1-infected donors had elevated frequencies of proapoptotic caspase-3(+) blood mDCs, and positive correlations were observed between caspase-3(+) mDC frequencies and plasma viral load and CD8(+) T-cell activation levels. Caspase-3(+) mDC frequencies, but not mDC Bcl-2 expression, were reduced with viral suppression on ART. Apoptosis markers on DCs in blood and LN samples from a cohort of untreated, HIV-1-infected donors with chronic disease were also evaluated. LN mDCs displayed higher levels of Bcl-2 and lower caspase-3(+) frequencies than did matched blood mDCs. Conversely, LN pDCs expressed lower Bcl-2 levels than their blood counterparts. In summary, blood mDCs from untreated HIV-1-infected subjects displayed a proapoptotic profile that was partially reversed with viral suppression, suggesting that DC death may be a factor contributing to blood DC depletion in the setting of chronic, untreated HIV disease.