Maintaining metabolic health is another important factor for having a healthy, well-functioning immune system. Under resting conditions, immune cells such as lymphocytes burn a combination of proteins, fats, and glucose for energy. During an active immune response, much of the fatty and amino acids that are utilized as fuel under resting conditions are instead used to synthesize proteins and lipids required for cell growth, causing an increased reliance on glucose metabolism for fuel.[1] The flexibility required to undergo this whole-sale metabolic shift from oxidative metabolism under resting conditions to glycolysis when the immune system becomes activated is an important factor for immune health. There is mounting evidence that immune cell function tends to suffer when “metabolic flexibility” is impaired.[2]
Healthy regulation of glucose homeostasis is key to ensuring adequate glucose supply to the cells and tissues that need it. When glucose homeostasis is impaired, the body is less able to maintain blood sugar levels within a healthy range, which can have negative effects on immune health. Many of the effects of impaired glucose homeostasis on immune health have been brought to light through research on type 2 diabetes (T2D): people with T2D are less able to fight off invading pathogens.[3] Hyperglycemia (abnormally high blood sugar) can also impair the immune response by affecting the immune system’s ability to induce[4] or resolve[5] inflammation. Glucose is a reactive molecule that causes chemical modifications to proteins if it is allowed to accumulate to toxic levels in the blood.[6] Animal studies have suggested that hyperglycemia may promote autoimmunity through the chemical modification of major histocompatibility complex (MHC) class II proteins in immune cells,[7] which play a role in sensing and responding to foreign pathogens. While further studies are needed to confirm these findings in humans, in the animal model, autoimmunity targeted a protein associated with cholesterol transport and atherosclerosis, suggesting a possible explanation for the connection between diabetes and atherosclerosis risk.[8]
References
- ^Kornberg MDThe immunologic Warburg effect: Evidence and therapeutic opportunities in autoimmunity.Wiley Interdiscip Rev Syst Biol Med.(2020-09)
- ^Nojima I, Eikawa S, Tomonobu N, Hada Y, Kajitani N, Teshigawara S, Miyamoto S, Tone A, Uchida HA, Nakatsuka A, Eguchi J, Shikata K, Udono H, Wada JDysfunction of CD8 + PD-1 + T cells in type 2 diabetes caused by the impairment of metabolism-immune axis.Sci Rep.(2020-09-10)
- ^Berbudi A, Rahmadika N, Tjahjadi AI, Ruslami RType 2 Diabetes and its Impact on the Immune System.Curr Diabetes Rev.(2020)
- ^Spindler MP, Ho AM, Tridgell D, McCulloch-Olson M, Gersuk V, Ni C, Greenbaum C, Sanda SAcute hyperglycemia impairs IL-6 expression in humans.Immun Inflamm Dis.(2016-Mar)
- ^Price CL, Hassi HO, English NR, Blakemore AI, Stagg AJ, Knight SCMethylglyoxal modulates immune responses: relevance to diabetes.J Cell Mol Med.(2010-Jun)
- ^Singh VP, Bali A, Singh N, Jaggi ASAdvanced glycation end products and diabetic complications.Korean J Physiol Pharmacol.(2014-Feb)
- ^Clement CC, Nanaware PP, Yamazaki T, Negroni MP, Ramesh K, Morozova K, Thangaswamy S, Graves A, Kim HJ, Li TW, Vigano' M, Soni RK, Gadina M, Tse HY, Galluzzi L, Roche PA, Denzin LK, Stern LJ, Santambrogio LPleiotropic consequences of metabolic stress for the major histocompatibility complex class II molecule antigen processing and presentation machinery.Immunity.(2021-04-13)
- ^Poznyak A, Grechko AV, Poggio P, Myasoedova VA, Alfieri V, Orekhov ANThe Diabetes Mellitus-Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation.Int J Mol Sci.(2020-Mar-06)