Palmer Clovis S, Anzinger Joshua J, Zhou Jingling, Gouillou Maelenn, Landay Alan, Jaworowski Anthony, McCune Joseph M, Crowe Suzanne M
Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3004, Australia;
Department of Microbiology, The University of the West Indies, Mona, Kingston 7, Jamaica, West Indies;
J Immunol. 2014 Dec 1;193(11):5595-603. doi: 10.4049/jimmunol.1303092. Epub 2014 Nov 3.
Monocyte activation during HIV-1 infection is associated with increased plasma levels of inflammatory markers and increased risk for premature development of age-related diseases. Because activated monocytes primarily use glucose to support cellular metabolism, we hypothesized that chronic monocyte activation during HIV-1 infection induces a hypermetabolic response with increased glucose uptake. To test this hypothesis, we evaluated glucose transporter 1 (Glut1) expression and glucose uptake by monocyte subpopulations in HIV-seropositive (HIV(+)) treatment-naive individuals (n = 17), HIV(+) individuals on combination antiretroviral therapy with viral loads below detection (n = 11), and HIV-seronegative (HIV(-)) individuals (n = 16). Surface expression of Glut1 and cellular uptake of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose were analyzed by flow cytometry on monocyte subpopulations. Irrespective of treatment status, monocytes from HIV(+) persons had significantly increased surface expression of Glut1 compared with those from HIV(-) controls. Nonclassical (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocyte subpopulations showed higher Glut1 expression than did classical (CD14(++)CD16(-)) monocytes. Intermediate monocytes from treatment-naive HIV(+) individuals also showed increased uptake of 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose compared with those from HIV(-) controls. Our results show that HIV infection is associated with increased glucose metabolism in monocytes and that Glut1 expression by proinflammatory monocytes is a potential marker of inflammation in HIV-infected subjects. However, the possibility exists whereby other Gluts such as Glut3 and Glut4 may also support the influx of glucose into activated and inflammatory monocyte populations.
HIV-1感染期间单核细胞的激活与炎症标志物血浆水平升高以及与年龄相关疾病过早发生的风险增加有关。由于活化的单核细胞主要利用葡萄糖来支持细胞代谢，我们推测HIV-1感染期间慢性单核细胞激活会诱导葡萄糖摄取增加的高代谢反应。为了验证这一假设，我们评估了未接受过治疗的HIV血清阳性（HIV(+)）个体（n = 17）、接受联合抗逆转录病毒治疗且病毒载量低于检测水平的HIV(+)个体（n = 11）以及HIV血清阴性（HIV(-)）个体（n = 16）中单核细胞亚群的葡萄糖转运蛋白1（Glut1）表达和葡萄糖摄取情况。通过流式细胞术分析单核细胞亚群上Glut1的表面表达以及荧光葡萄糖类似物2-(N-(7-硝基苯并-2-恶唑-1,3-二氮杂-4-基)氨基)-2-脱氧葡萄糖的细胞摄取。无论治疗状态如何，与HIV(-)对照组相比，HIV(+)个体的单核细胞Glut1表面表达显著增加。非经典（CD14(+)CD16(++)）和中间型（CD14(++)CD16(+)）单核细胞亚群的Glut1表达高于经典（CD14(++)CD16(-)）单核细胞。与HIV(-)对照组相比，未接受过治疗的HIV(+)个体的中间型单核细胞对2-(N-(7-硝基苯并-2-恶唑-1,3-二氮杂-4-基)氨基)-2-脱氧葡萄糖的摄取也增加。我们的结果表明，HIV感染与单核细胞中葡萄糖代谢增加有关，并且促炎单核细胞的Glut1表达是HIV感染受试者炎症的潜在标志物。然而，存在其他葡萄糖转运蛋白如Glut3和Glut4也可能支持葡萄糖流入活化和炎症单核细胞群体的可能性。
