Immune cell metabolism / Immunometabolism

Food is what humans eat or drink. It sustains life and growth (Oxford dictionary). Immune cells need energy. They need more when active or expanding. A new field, immunometabolism, has emerged. It shows nutrient availability affects immune cell function. This includes innate and specific immune memory.
Ye & Medzhitov 2019 Nat Metab 1(10): 947-957
Netea et al. 2020 Nat Rev Immunol 20(6): 375-388
Collins & Belkaid 2022 Immunity 55: 210-223

The diet's quality matters too. Vitamins, polyunsaturated fatty acids, and fiber influence the immune response. They affect immune cells directly. They also affect the gut microbiota and its metabolites indirectly. These include short-chain fatty acids and bile acid metabolites.
Verhasselt 2024 Immunol Rev 326: 117-129

Immunometabolism means that immune cell function is determined by metabolic status.
O'Neill & Pearce 2016 J. Exp. Med. 213: 15-23
Van den Bossche et al. 2017 Trends Immunol. 38: 395-406
Vrieling & Stienstra 2023 Trends in Immunology 44(3): 217

Fluctuating changes in the concentrations of metabolites in immune cells can influence the immune response
O’Neill et al. 2016
Makowski et al. 2020 Immunol Rev 295: 5.

Metabolism plays a crucial role in regulating the biology of conventional T cells (Tconv). Upon T Cell Receptor (TCR) engagement and the reception of co-stimulatory signals, a metabolic switch is triggered. This switch promotes the biosynthesis of nucleotides, fatty acids, and proteins, thereby increasing biomass to support cell proliferation and effector functions. These anabolic pathways are heavily dependent on enhanced glycolysis and glutaminolysis
Pearce et al. 2013 Science 342: 1242454

A key regulator of this metabolic switch is the mechanistic target of rapamycin (mTOR), a serine/threonine kinase. mTOR functions through its association with cofactors to form the mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2)
Laplante & Sabatini 2009 J Cell Sci 122: 3589-3594

Following TCR stimulation, mTOR is rapidly activated (Colombetti et al. 2006 J Immunol 176: 2730-2738) and is essential for the proliferation and function of Tconv. Conversely, inhibition of mTOR leads to T cell anergy (Zheng et al. 2007 J Immunol 178: 2163-2170; Zheng et al. 2009 J Immunol 183: 6095-6101).

Metabolic changes in immune cells are crucial. They determine specific immune responses. These changes are as important as signaling pathways. A key output is protein modification. This is done by metabolites. Glycolysis and Krebs cycle products mediate these events. Lipids, amino acids, and polyamines also play a role.
Diskin et al. 2020 Immunity 54: 19

A diverse set of Post-translational modifications (PTMs) in macrophages and T cells has been found. These alter phenotype. They modulate immunity and inflammation. This occurs in different contexts.
Diskin et al. 2020 Immunity 54: 19

Immunometabolism is a target to discover novel therapeutics for a wide range of diseases, including Cancer / Tumors, Autoimmune Diseases & Drugs/Treatments, and Metabolic Syndrome
Makowski et al. 2020 Immunol Rev 295: 5

Disturbances within the immune system occur in the form of infections, tumors, autoantigens.

In this process, immune cells change their metabolic activities. Various metabolic pathways are affected: glycolysis (pentose phosphate pathway); oxidative phosphorylation; beta-oxidation of fatty acids and transamination. The products of these cycles are integrated into the tricarboxylic acid cycle. However, many other pathways lead to many secondary metabolites that are not directly related to energy production or the maintenance of cell structure. These secondary metabolites can, act in ,an autocrine manner to retune immune cells and optimize their effector functions.
Chauhan et al. 2018

Normoxia supports the tricarboxylic acid (TCA) cycle and oxidative phosphorylation, whereas hypoxia leads to the activation of Hypoxia-inducible factor 1 alfa (HIF1A, HIF-1 alfa) and the expression of glycolytic enzymes. Stimulation of cells with interleukin-4 (IL-4) can induce oxidative phosphorylation, whereas the activation of cells through pattern recognition receptors (PRRs), such as Toll-like receptor 4 (TLR4), induces HIF1alfa expression to promote glycolysis.
O’Neill et al. 2016

Metabolic reprogramming helps the immune system deal with stress or changes from inside or outside the body. Macrophages, which are important parts of the immune system, need to change their metabolism in a specific way to work well.
O'Neill & Pearce 2016 J. Exp. Med. 213: 15-23

Activation of immune cells requires metabolic reprogramming
Pearce & Pearce 2013 Immunity 38(4): 633-643

see also:
Cancer / Tumors & Lactate / Lactic Acid
CD28
CD4+ CD25+ FOXP3 high Treg (peripherally induced) & Glycogen Synthase Kinase 3
Colitis / Intestinal Inflammation & Interleukin-10 (IL-10)
Food / Diets / Nutrients & Immunity
Immune System Activation
Macrophages (CD68s)
M1 macrophages (CD68+ iNOS+)
Metabolic Pathways