Changes in Glucose and Glutamine Lymphocyte Metabolisms Induced by Type I Interferon α

Abstract

In lymphocytes (LY), the well-documented antiproliferative effects of IFN-α are associated with inhibition of protein synthesis, decreased amino acid incorporation, and cell cycle arrest. However, the effects of this cytokine on the metabolism of glucose and glutamine in these cells have not been well investigated. Thus, mesenteric and spleen LY of male Wistar rats were cultured in the presence or absence of IFN-α, and the changes on glucose and glutamine metabolisms were investigated. The reduced proliferation of mesenteric LY was accompanied by a reduction in glucose total consumption (35%), aerobic glucose metabolism (55%), maximal activity of glucose-6-phosphate dehydrogenase (49%), citrate synthase activity (34%), total glutamine consumption (30%), aerobic glutamine consumption (20.3%) and glutaminase activity (56%). In LY isolated from spleen, IFNα also reduced the proliferation and impaired metabolism. These data demonstrate that in LY, the antiproliferative effects of IFNα are associated with a reduction in glucose and glutamine metabolisms.

Beta Interferon Regulation of Glucose Metabolism Is PI3K/Akt Dependent and Important for Antiviral Activity against Coxsackievirus B3

“…In contrast, our studies reflect a scenario of localized virus infection where cells in close proximity experience high concentrations of IFN-␣/␤ produced by tissue-resident cells or plasmacytoid dendritic cells during an acute immune response to virus infection. In other studies, Navarro et al examined the effects of type I IFN treatment on glucose metabolism in primary mesenteric and splenic lymphocytes after 48 h and likewise showed a suppression of glucose uptake (72). Notably, in the earliest IFN experiments of Isaacs and Lindenmann, conducted in chicken embryo cells, they identified a modest IFN-inducible effect on lactate production after 4 h, an indicator of glycolysis (73).…”

Metabolic Regulation of T Lymphocytes

“…In exhaustion, however, T cells have reduced production of IL-2, and this may contribute to reduced glucose metabolism of exhausted T cells (103). Navarro et al (111) demonstrated that, unlike IL-2, the antiviral cytokine type I IFN member IFN- α diminished glucose and glutamine metabolism in activated lymphocytes. This defect was characterized by decreased activity of the metabolic enzymes glucose-6-phosphate dehydrogenase (G6PDH), citrate synthase, and phosphate-dependent glutaminase.…”

Blocking inflammation to improve immunotherapy of advanced cancer

“…33 Persistent activation of macrophages by neoplastic cells does not favor sustained antitumor T-cell responses. [34][35][36][37][38] This may be exacerbated by IFN-c-associated with Treg reprogramming, which specifically polarizes tumor-associated macrophages into an M1 pro-inflammatory phenotype. 39,40 This is characterized by increased synthesis of IL-6, production of reactive oxygen species (ROS), specific changes of glucose metabolism and a capacity to modulate iron metabolism.…”

“…Several in vivo and in vitro experimental models involving Treg reprogramming into IFN‐ γ ‐producing cells, have shown that loss of Treg cell activity is accompanied by pro‐inflammatory polarization of peritoneal macrophages with associated release of pro‐inflammatory and immunosuppressive cytokines . Persistent activation of macrophages by neoplastic cells does not favor sustained anti‐tumor T‐cell responses . This may be exacerbated by IFN‐ γ ‐associated with Treg reprogramming, which specifically polarizes tumor‐associated macrophages into an M1 pro‐inflammatory phenotype .…”