Biochemical Underpinnings of Immune Cell Metabolic Phenotypes

Abstract

The metabolism of immune cells affects their function and influences host immunity. This review explores how immune cell metabolic phenotypes reflect biochemical dependencies, and highlights evidence that the metabolic state of immune cells and nutrient availability can both alter immune responses. The central importance of oxygen, energetics, and redox homeostasis in immune cell metabolism, and how these factors are reflected in different metabolic phenotypes, is also discussed. Linking immune cell metabolic phenotype to effector functions is important to understand how altering metabolism can impact the way in which immune cells meet their metabolic demands and affect the immune response in various disease contexts.

Fatty acid metabolism in CD8+ T cell memory: Challenging current concepts

“…It is likely that T cells differentiated in vitro with IL-15 will not share all features of long-lived CD8 + T mem cells obtained after an infection, as IL-15 is not the only factor that influences their development in vivo . In addition, as it has been pointed out (130), the concentration of nutrients such as glucose, lipids, glutamine or O 2 that lymphocytes are exposed to in cell culture medium is radically different to that encountered in vivo , and thus limit the application of the information obtained from cell cultures into a real infection setting (159). …”

“…This is supported by the fact that CD8 + T cells lacking CPT1A are capable of differentiating into T eff cells after TCR stimulation in vitro and after bacterial infection in vivo (25). However, in vivo studies suggest that OxPhos and FAO can play important roles in disease models that involve chronic stimulation with self-antigen or T cell exhaustion during chronic infection or tumour responses (19, 158, 159). T cells activated in vivo by MHC alloantigens as in the case of graft-versus-host disease (GVHD) seem to not upregulate Glut1 and display an increased OCR and mitochondrial membrane potential (160).…”

Microglia and sexual differentiation of the developing brain: A focus on ontogeny and intrinsic factors

“…As the major regulators of cellular energy metabolism, cell death, and the maintenance of calcium and redox homeostasis, mitochondria are uniquely positioned to modulate the innate immune response (Mills, Kelly, & O'Neill, ). Indeed, emerging literature suggests an intimate link between the metabolic state of immune cells and their differentiation and activation (Olenchock, Rathmell, & Vander Heiden, ). While research into immunometabolic states of microglia is still in its infancy, characterization of closely related macrophages has recently begun to flourish.…”

MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells

“…These transitions involve large-scale changes in gene expression and therefore of cellular function and may irreversibly change fate and lifespan expectancy. Recent work has established that enactment of these events requires substantial metabolic reprogramming (Buck et al, 2015; O’Neill and Pearce, 2016; Pearce et al, 2013), and this, as well as the realization that living in diverse tissue-specific niches may have metabolic consequences for immune cells, is serving to refocus attention on immune cell metabolism (for detailed discussion of bioenergetics in immune cell, please see Olenchock et al, 2017, in this issue). Integral to this area of research is the question of how immune cells assess their metabolic status.…”