A guide to immunometabolism for immunologists

Abstract

In recent years a substantial number of findings have been made in the area of immunometabolism, by which we mean the changes in intracellular metabolic pathways in immune cells that alter their function. Here, we provide a brief refresher course on six of the major metabolic pathways involved (specifically, glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, fatty acid oxidation, fatty acid synthesis and amino acid metabolism), giving specific examples of how precise changes in the metabolites of these pathways shape the immune cell response. What is emerging is a complex interplay between metabolic reprogramming and immunity, which is providing an extra dimension to our understanding of the immune system in health and disease.

Immunometabolism: Is it under the eye of the clock?

“…The presence of circadian rhythms in metabolic pathways has also been described [32]. In recent years, realisation that the metabolic state of immune cells can contribute to their immune phenotype has lead to the emergence of a new field called immunometabolism [33]. Therefore the clock may intersect with immunity and metabolism via the axis of immunometabolism, possibly opening up a new body of study, circadian immunometabolism.…”

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

“…Imbalances in common metabolites have been shown to affect immune functions. 153 In P. falciparum malaria, an increase in permeability of an immortalized brain endothelial cell line (hCMEC/D3) was shown to occur in an acidic environment attributed to parasite metabolic products. 45 As metabolic acidosis secondary to lactate production by both host and parasites is one of the main indicators of a poor outcome of severe malaria 36 lactic acid too could contribute to barrier dysfunction.…”

Immunophysiology: Macrophages as key regulators of homeostasis in various organs

“…Then, Schultze and Aschenbrenner summarize recent evidence on how transcriptional regulatory networks render the inherently autonomous macrophages capable of responding to different tissue microenvironmental cues, ultimately enabling them to serve as accessory cells in diverse organs. While it is accepted that distinct intracellular metabolic pathways determine the function of immune cells (Bimmunometabolism^) [3], we are only beginning to understand that macrophages play a key role in governing whole body metabolism as well. In particular, macrophages drive obesity-induced metaflammation which interferes with the metabolic effects of insulin.…”