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

Palmer CS, Anzinger JJ, Zhou J, Gouillou M, Landay A, Jaworowski A, McCune JM, Crowe SM
Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3004, Australia; cpalmer@burnet.edu.au.

Abstract

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.

This work was supported by the Australian Centre for HIV and Hepatitis Virology Research; a 2010 developmental grant (Creative and Novel Ideas in HIV Research) from the University of Washington Center for AIDS Research; a National Institutes of Health–funded program under Award AI027757, which is supported by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Institute of Mental Health, the National Institute on Drug Abuse, the National Institute of Child Health and Human Development, the National Heart, Lung, and Blood Institute, and the National Institute on Aging; Creative and Novel Ideas in HIV Research and the Australian Centre for HIV and Hepatitis Virology Research (to C.S.P); and a National Health and Medical Research Council of Australia Principal Research Fellowship (to S.M.C.).

Full text of this article can be obtained from the publisher’s web site at

http://www.jimmunol.org/content/193/11/5595.long

Publication

  • Journal: Journal of Immunology
  • Published: 03/11/2014
  • Volume: 193
  • Issue: 11
  • Pagination: 5595-5603

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