Glucose Transporter 1–Expressing Proinflammatory Monocytes Are Elevated in Combination Antiretroviral Therapy–Treated and Untreated HIV+ Subjects

• Published in: The Journal of immunology (1950) Vol. 193; no. 11; pp. 5595 - 5603
• Main Authors: Palmer, Clovis S, Anzinger, Joshua J, Zhou, Jingling, Gouillou, Maelenn, Landay, Alan, Jaworowski, Anthony, McCune, Joseph M, Crowe, Suzanne M
• Format: Journal Article
• Language: English
• Published: United States 01.12.2014
• Subjects: Adult; Aged; Anti-Retroviral Agents - administration & dosage; Anti-Retroviral Agents - adverse effects; Australia; Biomarkers - metabolism; Drug Combinations; Female; Glucose - analogs & derivatives; Glucose - metabolism; Glucose Transporter Type 1 - genetics; Glucose Transporter Type 1 - metabolism; HIV - immunology; HIV Infections - immunology; HIV Infections - therapy; HIV Seropositivity; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Inflammation Mediators - metabolism; Male; Middle Aged; Monocytes - drug effects; Monocytes - immunology; Monocytes - virology; Up-Regulation; Australia
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1303092

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.