Abstract
Objective:Immune dysfunction and chronic inflammation are characteristic of HIV infection and diabetes mellitus, with CD4+T-cell metabolism implicated in the pathogenesis of each disease. However, there is limited information on CD4+T-cell metabolism in HIV+ persons with diabetes mellitus. We examined CD4+T-cell glucose metabolism in HIV+ women with and without diabetes mellitus.Design:A case-control study was used to compare CD4+T-cell glucose metabolism in women with HIV with or without diabetes mellitus.Methods:Nondiabetic (HIV+DM-, N = 20) or type 2 diabetic HIV+ women with (HIV+DM+, N = 16) or without (HIV+DMTx+, N = 18) antidiabetic treatment were identified from the WIHS and matched for age, race/ethnicity, smoking status and CD4+cell count. CD4+T-cell immunometabolism was examined by flow cytometry, microfluidic qRT-PCR of metabolic genes, and Seahorse extracellular flux analysis of stimulated CD4+T cells.Results:HIV+DM+ displayed a significantly elevated proportion of CD4+T cells expressing the immunometabolic marker GLUT1 compared with HIV+DMTx+ and HIV+DM- (P = 0.04 and P = 0.01, respectively). Relative expression of genes encoding key enzymes for glucose metabolism pathways were elevated in CD4+T cells of HIV+DM+ compared with HIV+DMTx+ and HIV+DM-. T-cell receptor (TCR)-activated CD4+T cells from HIV+DM+ showed elevated glycolysis and oxidative phosphorylation compared with HIV+DM-.Conclusion:CD4+T cells from HIV+DM+ have elevated glucose metabolism. Treatment of diabetes mellitus among women with HIV may partially correct CD4+T-cell metabolic dysfunction.
Original language | English (US) |
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Pages (from-to) | 1327-1336 |
Number of pages | 10 |
Journal | AIDS |
Volume | 36 |
Issue number | 10 |
DOIs | |
State | Published - Aug 1 2022 |
Externally published | Yes |
Keywords
- CD4T cells
- HIV
- diabetes mellitus
- immunometabolism
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases