title: Glucose transporter 1-expressing proinflammatory monocytes are elevated in combination antiretroviral therapy-treated and untreated HIV+ subjects.
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.
authors.affiliation: Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3004, Australia; cpalmer@burnet.edu.au.
authors.forename: Clovis S
authors.initials: CS
authors.lastname: Palmer
authors.affiliation: Department of Microbiology, The University of the West Indies, Mona, Kingston 7, Jamaica, West Indies;
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Anzinger
authors.affiliation: Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3004, Australia;
authors.forename: Jingling
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3004, Australia;
authors.forename: Maelenn
authors.initials: M
authors.lastname: Gouillou
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612;
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.affiliation: Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3004, Australia; Department of Infectious Diseases, Monash University, Melbourne, Victoria 3800, Australia; Department of Immunology, Monash University, Melbourne, Victoria 3004, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Jaworowski
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143; and.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
authors.affiliation: Centre for Biomedical Research, Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria 3004, Australia; Department of Infectious Diseases, Monash University, Melbourne, Victoria 3800, Australia; Department of Medicine, Monash University, Melbourne, Victoria, Australia 3800.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Crowe
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D001315:Australia; D015415:Biomarkers / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D005947:Glucose / Q000031:analogs & derivatives / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D006679:HIV Seropositivity; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D015854:Up-Regulation
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D004338:Drug Combinations; D051272:Glucose Transporter Type 1; D018836:Inflammation Mediators; D005947:Glucose