Publications & Reports

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

Butterfield TR, Hanna DB, Kaplan RC, Xue X, Kizer JR, Durkin HG, Kassaye SG, Nowicki M, Tien PC, Golub ET, Floris-Moore MA, Titanji K, Fischl MA, Heath S, Palmer CS, Landay AL, Anzinger JJ
Department of Microbiology, University of the West Indies - Mona, Kingston.

Abstract

OBJECTIVE: Immune dysfunction and chronic inflammation are characteristic of HIV infection and diabetes mellitus (DM), 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 DM. We examined CD4+ T cell glucose metabolism in HIV+ women with and without DM. DESIGN: A case-control study was used to compare CD4+ T cell glucose metabolism in women with HIV with or without DM. METHODS: Non-diabetic (HIV+DM-, N = 20) or type 2 diabetic HIV+ women with (HIV+DM+, N = 16) or without (HIV+DMTx+, N = 18) anti-diabetic treatment were identified from the WIHS and matched for age, race/ethnicity, smoking status and CD4 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 to 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 to HIV+DMTx+ and HIV+DM-. TCR-activated CD4+ T cells from HIV+DM+ showed elevated glycolysis and oxidative phosphorylation compared to HIV+DM-. CONCLUSIONS: CD4+ T cells from HIV+DM+ have elevated glucose metabolism. Treatment of DM among women with HIV may partially correct CD4+ T cell metabolic dysfunction.

Link to publisher’s web site

Publication

  • Journal: AIDS
  • Published: 21/06/2022
  • Volume: 36
  • Issue: 10
  • Pagination: 1327-1336