Glucose transporter 1-expressing proinflammatory monocytes are elevated in combination antiretroviral therapy-treated and untreated HIV+ subjects

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 chronicmonocyte activation duringHIV-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 HIVseropositive (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 ofGlut1 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. Copyright ? 2014 by The American Association of Immunologists, Inc