Glycolysis – a key player in the inflammatory response

Abstract

The inflammatory response involves the activation of several cell types to fight insults caused by a plethora of agents, and to maintain the tissue homoeostasis. On the one hand, cells involved in the pro-inflammatory response, such as inflammatory M1 macrophages, Th1 and Th17 lymphocytes or activated microglia, must rapidly provide energy to fuel inflammation, which is essentially accomplished by glycolysis and high lactate production. On the other hand, regulatory T cells or M2 macrophages, which are involved in immune regulation and resolution of inflammation, preferentially use fatty acid oxidation through the TCA cycle as a main source for energy production. Here, we discuss the impact of glycolytic metabolism at the different steps of the inflammatory response. Finally, we review a wide variety of molecular mechanisms which could explain the relationship between glycolytic metabolites and the pro-inflammatory phenotype, including signalling events, epigenetic remodelling, post-transcriptional regulation and post-translational modifications. Inflammatory processes are a common feature of many age-associated diseases, such as cardiovascular and neurodegenerative disorders. The finding that immunometabolism could be a master regulator of inflammation broadens the avenue for treating inflammation-related pathologies through the manipulation of the vascular and immune cell metabolism.

Mitophagy in Human Diseases

“…Proinflammatory response by immune cells (M1 macrophages, Th1 and Th17 lymphocytes, dendritic cells, and microglia) is linked to high levels of anaerobic glycolysis, while M2 macrophages and regulatory T cells rely heavily on mitochondrial OXPHOS metabolism [ 407 ]. Mitophagy contributes to the regulated metabolic switch towards glycolysis in M1 macrophage polarization in an NIX-mediated manner [ 408 ]. Additionally, a loss of PINK1 induces proinflammatory markers in glial cells, suggesting a protective role for mitophagy in inflammation [ 409 ].…”

Systemic Inflammation and COVID-19 Mortality in Patients with Major Noncommunicable Diseases: Chronic Coronary Syndromes, Diabetes and Obesity

“…Of course, there are various intermediate phenotypes, as macrophages are a heterogeneous cell population [ 94 ]. The same distinctive metabolic profiles are exhibited by other cell types involved in the inflammatory response, i.e., Th1, Th17 cells, activated microglia or endothelial cells, which produce highly demanded energy through glycolysis upon inflammation, while regulatory T cells (Tregs), memory T cells and resting microglia rely on fatty acid oxidation to maintain tissue homeostasis [ 98 , 99 ]. The effector T cells (as well as M1 macrophages) express high levels of glucose transporter 1 (GLUT1) and are highly glycolytic, while the Treg express low levels of GLUT1 [ 99 ].…”

Automated Spatially Targeted Optical Micro Proteomics (AutoSTOMP) 2.0 identifies proteins enriched within inflammatory lesions in tissue sections and human clinical biopsies

“…Most of the enriched pathways were characterized by the abundance of proteasome components detected in the IgG4 lesions (Figure S-6A, asterisks). Independent of this proteasome signature, glycolytic metabolic pathways were the most highly represented GO-terms in the ‘IgG4’ fraction, consistent with metabolic demands needed to drive an inflammatory response (Figure S-6, red) 36 . By contrast, the ‘flow through’ fraction was enriched in proteins regulating epithelial turnover and differentiation (Figure S-6, blue) 37 .…”