Immunometabolism and the modulation of immune responses and host defense: A role for methylglyoxal?

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2022-08, Vol.1868 (8), p.166425-166425, Article 166425
• Main Authors: Zhang, Xiaodi, Schalkwijk, Casper G., Wouters, Kristiaan
• Format: Article
• Language: English
• Subjects: Advanced glycation endproducts; Diabetes Mellitus, Type 2 - metabolism; Humans; Hyperglycemia; Immunity; Immunometabolism; Insulin Resistance; Leukocytes; Magnesium Oxide; Methylglyoxal; Pyruvaldehyde - metabolism
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2022.166425

The immune system plays an essential role in protecting the body against pathogens. Immune cells are activated during infections, resulting in a metabolic shift from oxidative phosphorylation to glycolysis. During glycolysis, methylglyoxal (MGO) can be formed as a by-product. As a highly reactive dicarbonyl compound, MGO can rapidly react with proteins to form advanced glycation end products (AGEs). MGO and MGO-derived AGEs have been implicated in the development of insulin resistance, type 2 diabetes and its complications and several other age-related inflammatory diseases. MGO has been found in adipose tissue, atherosclerosis plaques and inflamed livers. Aside from the potential harmful role of MGO, there are studies showing beneficial effects of MGO as a defense mechanism during infections and diseases. In this review, we summarize anti-microbial effects of MGO and the link between MGO and immune cell activation, as potential mediator during host defense. •Immune cell activation is associated with enhanced glycolysis, leading to the formation of the reactive dicarbonyl methylglyoxal (MGO).•MGO rapidly leads to the formation of protein adducts and is cytotoxic.•MGO has direct anti-microbial effects and immunomodulatory effects.•The extent of MGO production in immune cells and its contribution to host defense remain to be further elucidated.