Changing the energy of an immune response

Abstract

The breakdown of nutrients into the critical energy source ATP is the general purpose of cellular metabolism and is essential for sustaining life. Similarly, the immune system is composed of different cell subsets that are indispensable for defending the host against pathogens and disease. The interplay between metabolic pathways and immune cells leads to a plethora of different signaling pathways as well as cellular activities. The activation of T cells via glycolysis-mediated upregulation of surface markers, for example, is necessary for an appropriate effector response against an infection. However, tight regulation of immune cell metabolism is required for protecting the host and resuming homeostasis. An imbalance of immunological metabolic function and/or metabolic byproducts (reactive oxygen species) can oftentimes lead to diseases. In the case of cancer, overactive glucose metabolism can lead to hyperproliferation of cells and subsequent decreases in cytotoxic T cell activity, which attack and destroy the tumor. For this reason and many more, targeting metabolism in immune cells may be a novel therapeutic strategy for treatment of disease. The metabolic pathways of immune cells and the possibilities of immunometabolic therapies will be discussed.

Keywords: Metabolism; aerobic glycolysis; immune response; oxidative phosphorylation.

Figure 1

Lymphocyte metabolism fluctuation during resting and activated states. Quiescent, or resting, lymphocytes primarily utilize oxidative phosphorylation to build up reserves of ATP in preparation for activation. Activated, or proliferating, lymphocytes predominately use aerobic glycolysis due to its rapid speed and critical role in forming biosynthetic precursors.

Figure 2

Metabolic modulation potential of manganese porphyrins. Manganese porphyrins, or catalytic antioxidants, have been shown to decrease NF-κB and HIF-1 activation, reduce T cell-mediated type 1 diabetes progression/onset, and maintain islet cell function during isolation and transplantation. Proposed metabolic effects of metalloporphyrins include decreasing: cell growth, hypoxia-induced reperfusion injury, the Warburg effect, and bioenergetics of diabetogenic immune cells.