Elevated CD4+T-cell glucose metabolism in HIV+ women with diabetes mellitus

Tiffany R. Butterfield, David B. Hanna, Robert C. Kaplan, Xiaonan Xue, Jorge R. Kizer, Helen G. Durkin, Seble G. Kassaye, Marek Nowicki, Phyllis C. Tien, Elizabeth T. Topper, Michelle A. Floris-Moore, Kehmia Titanji, Margaret A. Fischl, Sonya Heath, Clovis S. Palmer, Alan L. Landay, Joshua J. Anzinger

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)1327-1336
Number of pages10
JournalAIDS
Volume36
Issue number10
DOIs
StatePublished - Aug 1 2022
Externally publishedYes

Keywords

  • CD4T cells
  • diabetes mellitus
  • HIV
  • immunometabolism

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Elevated CD4+T-cell glucose metabolism in HIV+ women with diabetes mellitus'. Together they form a unique fingerprint.

Cite this