Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Perspective

Hyperglycemia-Induced Immune System Disorders in Diabetes Mellitus and the Concept of Hyperglycemic Memory of Innate Immune Cells: A Perspective

Author(s): Giuseppe Lisco, Vito Angelo Giagulli, Giovanni De Pergola, Edoardo Guastamacchia, Emilio Jirillo* and Vincenzo Triggiani

Volume 22, Issue 4, 2022

Published on: 20 January, 2022

Page: [367 - 370] Pages: 4

DOI: 10.2174/1871530321666210924124336

Abstract

A wealth of information suggests that hyperglycemia plays a paramount role in diabetes- related chronic complications. Notably, in Type 2 Diabetes Mellitus (T2DM), a persistent condition of hyperglycemia and altered insulin signaling seems to account for a status of chronic low-grade inflammation. This systemic inflammatory condition, in turn, depends on the profound impairment of the immune machinery, especially in some corporeal districts such as the adipose tissue, pancreatic islets, endothelia, and circulating leukocytes. Interestingly, poor glycemic control has been associated with cardiac autoimmunity in patients with Type 1 Diabetes (T1DM), and cardiac autoantibody positivity is associated with an increased risk of Cardiovascular Diseases (CVD) decades later. This condition also suggests a role for autoimmune mechanisms in CVD development in patients with T1DM, possibly through inflammatory pathways. Evidence has been provided for an elevated release of cytokines, such as interleukin (IL)-1 beta and IL-6, as well as chemokines (C-C motif Ligand 2 and IL-8). Of note, these mediators are responsible for abnormal leukocyte trafficking into many tissues, contributing to insulin resistance, reduced insulin secretion, and vascular complications. In fact, hyperglycemia in individuals with diabetes mellitus is associated with higher circulating E-selectin, soluble Cell Adhesion Molecule (sCAM)-1, and vascular CAM-1 compared to normoglycemic healthy volunteers. Therefore, patients with diabetes mellitus exhibit an exaggerated adhesion of leukocytes to endothelia, and this phenomenon is related to hyperglycemia. The increased production of advanced glycosylation end products or AGEs activates a further cascade of noxious events with a massive generation of Reactive Oxygen Radicals (ROS) and enhanced expression of CAMs.

Keywords: Diabetes mellitus, hyperglycemia, hyperglycemic memory, epigenetics, inflammation, trained immunity.

Next »
[1]
Holman, R.R.; Paul, S.K.; Bethel, M.A.; Matthews, D.R.; Neil, H.A. 10-year follow-up of intensive glucose control in type 2 diabetes. N. Engl. J. Med., 2008, 359(15), 1577-1589.
[http://dx.doi.org/10.1056/NEJMoa0806470] [PMID: 18784090]
[2]
Egaña-Gorroño, L.; López-Díez, R.; Yepuri, G.; Ramirez, L.S.; Reverdatto, S.; Gugger, P.F.; Shekhtman, A.; Ramasamy, R.; Schmidt, A.M. Receptor for advanced glycation end products (RAGE) and mechanisms and therapeutic opportunities in diabetes and cardiovascular disease: Insights from human subjects and animal models. Front. Cardiovasc. Med., 2020, 7, 37.
[http://dx.doi.org/10.3389/fcvm.2020.00037] [PMID: 32211423]
[3]
Sousa, G.R.; Pober, D.; Galderisi, A.; Lv, H.; Yu, L.; Pereira, A.C.; Doria, A.; Kosiborod, M.; Lipes, M.A. Glycemic control, cardiac autoimmunity, and long-term risk of cardiovascular disease in type 1 diabetes mellitus. Circulation, 2019, 139(6), 730-743.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036068] [PMID: 30586738]
[4]
Pezhman, L.; Tahrani, A.; Chimen, M. Dysregulation of leukocyte trafficking in type 2 diabetes: Mechanisms and potential therapeutic avenues. Front. Cell Dev. Biol., 2021, 96 , 21484.
[http://dx.doi.org/10.3389/fcell.2021.624184] [PMID: 33692997]
[5]
Lopez-Candales, A.; Hernández Burgos, P.M.; Hernandez-Suarez, D.F.; Harris, D. Linking chronic inflammation with cardiovascular disease: From normal aging to the metabolic syndrome. J. Nat. Sci., 2017, 3(4), e341.
[PMID: 28670620]
[6]
Eguchi, K.; Nagai, R. Islet inflammation in type 2 diabetes and physiology. J. Clin. Invest., 2017, 127(1), 14-23.
[http://dx.doi.org/10.1172/JCI88877] [PMID: 28045399]
[7]
Cook-Mills, J.M.; Marchese, M.E.; Abdala-Valencia, H. Vascular cell adhesion molecule-1 expression and signaling during disease: Regulation by reactive oxygen species and antioxidants. Antioxid. Redox Signal., 2011, 15(6), 1607-1638.
[http://dx.doi.org/10.1089/ars.2010.3522] [PMID: 21050132]
[8]
Takeuchi, M.; Sakasai-Sakai, A.; Takata, T.; Takino, J.I.; Koriyama, Y.; Kikuchi, C.; Furukawa, A.; Nagamine, K.; Hori, T.; Matsunaga, T. Intracellular toxic agEs (TAGE) triggers numerous types of cell damage. Biomolecules, 2021, 11(3), 387.
[http://dx.doi.org/10.3390/biom11030387] [PMID: 33808036]
[9]
Wouters, K.; Gaens, K.; Bijnen, M.; Verboven, K.; Jocken, J.; Wetzels, S.; Wijnands, E.; Hansen, D.; van Greevenbroek, M.; Duijvestijn, A.; Biessen, E.A.; Blaak, E.E.; Stehouwer, C.D.; Schalkwijk, C.G. Circulating classical monocytes are associated with CD11c+ macrophages in human visceral adipose tissue. Sci. Rep., 2017, 7, 42665.
[http://dx.doi.org/10.1038/srep42665] [PMID: 28198418]
[10]
Huang, J.; Xiao, Y.; Zheng, P.; Zhou, W.; Wang, Y.; Huang, G.; Xu, A.; Zhou, Z. Distinct neutrophil counts and functions in newly diagnosed type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes. Diabetes Metab. Res. Rev., 2019, 35(1), , e3064..
[http://dx.doi.org/10.1002/dmrr.3064] [PMID: 30123986]
[11]
Talukdar, S.; Oh, D.Y.; Bandyopadhyay, G.; Li, D.; Xu, J.; McNelis, J.; Lu, M.; Li, P.; Yan, Q.; Zhu, Y.; Ofrecio, J.; Lin, M.; Brenner, M.B.; Olefsky, J.M. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat. Med., 2012, 18(9), 1407-1412.
[http://dx.doi.org/10.1038/nm.2885] [PMID: 22863787]
[12]
Musilli, C.; Paccosi, S.; Pala, L.; Gerlini, G.; Ledda, F.; Mugelli, A.; Rotella, C.M.; Parenti, A. Characterization of circulating and monocyte-derived dendritic cells in obese and diabetic patients. Mol. Immunol., 2011, 49(1-2), 234-238.
[http://dx.doi.org/10.1016/j.molimm.2011.08.019] [PMID: 21940050]
[13]
Mráz, M.; Cinkajzlová, A.; Kloučková, J.; Lacinová, Z.; Kratochvílová, H.; Lipš, M.; Pořízka, M.; Kopecký, P.; Lindner, J.; Kotulák, T.; Netuka, I.; Haluzík, M. Dendritic cells in subcutaneous and epicardial adipose tissue of subjects with type 2 diabetes, obesity, and coronary artery disease. Mediators Inflamm., 2019, 2019, , 5481725..
[http://dx.doi.org/10.1155/2019/5481725] [PMID: 31210749]
[14]
Chen, Y.; Tian, J.; Tian, X.; Tang, X.; Rui, K.; Tong, J.; Lu, L.; Xu, H.; Wang, S. Adipose tissue dendritic cells enhances inflammation by prompting the generation of Th17 cells. PLoS One, 2014, 9(3), , e92450..
[http://dx.doi.org/10.1371/journal.pone.0092450] [PMID: 24642966]
[15]
Zhou, T.; Hu, Z.; Yang, S.; Sun, L.; Yu, Z.; Wang, G. Role of adaptive and innate immunity in type 2 diabetes mellitus. J. Diabetes Res., 2018, 2018, , 7457269..
[http://dx.doi.org/10.1155/2018/7457269] [PMID: 30533447]
[16]
Yuan, N.; Zhang, H.F.; Wei, Q.; Wang, P.; Guo, W.Y. Expression of CD4+CD25+Foxp3+ regulatory T cells, interleukin 10 and transforming growth factor β in newly diagnosed type 2 diabetic patients. Exp. Clin. Endocrinol. Diabetes, 2018, 126(2), 96-101.
[http://dx.doi.org/10.1055/s-0043-113454] [PMID: 28954308]
[17]
Jagannathan-Bogdan, M.; McDonnell, M.E.; Shin, H.; Rehman, Q.; Hasturk, H.; Apovian, C.M.; Nikolajczyk, B.S. Elevated proinflammatory cytokine production by a skewed T cell compartment requires monocytes and promotes inflammation in type 2 diabetes. J. Immunol., 2011, 186(2), 1162-1172.
[http://dx.doi.org/10.4049/jimmunol.1002615] [PMID: 21169542]
[18]
Feuerer, M.; Herrero, L.; Cipolletta, D.; Naaz, A.; Wong, J.; Nayer, A.; Lee, J.; Goldfine, A.B.; Benoist, C.; Shoelson, S.; Mathis, D. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat. Med., 2009, 15(8), 930-939.
[http://dx.doi.org/10.1038/nm.2002] [PMID: 19633656]
[19]
Cao, Y.L.; Zhang, F.Q.; Hao, F.Q. Th1/Th2 cytokine expression in diabetic retinopathy. Genet. Mol. Res., 2016, 15(3), 15.
[http://dx.doi.org/10.4238/gmr.15037311] [PMID: 27525838]
[20]
Magrone, T.; Jirillo, E.; Spagnoletta, A.; Magrone, M.; Russo, M.A.; Fontana, S.; Laforgia, F.; Donvito, I.; Campanella, A.; Silvestris, F.; De Pergola, G. Immune profile of obese people and In Vitro effects of red grape polyphenols on peripheral blood mononuclear cells. Oxid. Med. Cell. Longev., 2017, 2017, , 9210862..
[http://dx.doi.org/10.1155/2017/9210862] [PMID: 28243360]
[21]
Luc, K.; Schramm-Luc, A.; Guzik, T.J.; Mikolajczyk, T.P. Oxidative stress and inflammatory markers in prediabetes and diabetes. J. Physiol. Pharmacol., 2019, 70(6), , 809--824..
[http://dx.doi.org/10.26402/jpp.2019.6.01] [PMID: 32084643]
[22]
Cencioni, C.; Spallotta, F.; Greco, S.; Martelli, F.; Zeiher, A.M.; Gaetano, C. Epigenetic mechanisms of hyperglycemic memory. Int. J. Biochem. Cell Biol., 2014, 51, 155-158.
[http://dx.doi.org/10.1016/j.biocel.2014.04.014] [PMID: 24786298]
[23]
Ahmed, S.M.; Johar, D.; Ali, M.M.; El-Badri, N. Insights into the role of DNA methylation and protein misfolding in diabetes mellitus. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19(6), 744-753.
[http://dx.doi.org/10.2174/1871530319666190305131813] [PMID: 30834843]
[24]
Thiem, K.; Keating, S.T.; Netea, M.G.; Riksen, N.P.; Tack, C.J.; van Diepen, J.; Stienstra, R. Hyperglycemic memory of innate immune cells promotes In Vitro Proinflammatory Responses of Human Monocytes and Murine Macrophages. J. Immunol., 2021, 206(4), 807-813.
[http://dx.doi.org/10.4049/jimmunol.1901348] [PMID: 33431659]
[25]
Cheng, S.C.; Quintin, J.; Cramer, R.A.; Shepardson, K.M.; Saeed, S.; Kumar, V.; Giamarellos-Bourboulis, E.J.; Martens, J.H.; Rao, N.A.; Aghajanirefah, A.; Manjeri, G.R.; Li, Y.; Ifrim, D.C.; Arts, R.J.; van der Veer, B.M.; Deen, P.M.; Logie, C.; O’Neill, L.A.; Willems, P.; van de Veerdonk, F.L.; van der Meer, J.W.; Ng, A.; Joosten, L.A.; Wijmenga, C.; Stunnenberg, H.G.; Xavier, R.J.; Netea, M.G. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science, 2014, 345(6204), , 1250684..
[http://dx.doi.org/10.1126/science.1250684] [PMID: 25258083]
[26]
Nagareddy, P.R.; Murphy, A.J.; Stirzaker, R.A.; Hu, Y.; Yu, S.; Miller, R.G.; Ramkhelawon, B.; Distel, E.; Westerterp, M.; Huang, L.S.; Schmidt, A.M.; Orchard, T.J.; Fisher, E.A.; Tall, A.R.; Goldberg, I.J. Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab., 2013, 17(5), 695-708.
[http://dx.doi.org/10.1016/j.cmet.2013.04.001] [PMID: 23663738]
[27]
Christ, A.; Günther, P.; Lauterbach, M.A.R.; Duewell, P.; Biswas, D.; Pelka, K.; Scholz, C.J.; Oosting, M.; Haendler, K.; Baßler, K.; Klee, K.; Schulte-Schrepping, J.; Ulas, T.; Moorlag, S.J.C.F.M.; Kumar, V.; Park, M.H.; Joosten, L.A.B.; Groh, L.A.; Riksen, N.P.; Espevik, T.; Schlitzer, A.; Li, Y.; Fitzgerald, M.L.; Netea, M.G.; Schultze, J.L.; Latz, E. Western diet triggers NLRP3-Dependent innate immune reprogramming. Cell, 2018, 172(1-2), 162-175.e14.
[http://dx.doi.org/10.1016/j.cell.2017.12.013] [PMID: 29328911]
[28]
Keating, S.T.; Groh, L.; Thiem, K.; Bekkering, S.; Li, Y.; Matzaraki, V.; van der Heijden, C.D.C.C.; van Puffelen, J.H.; Lachmandas, E.; Jansen, T.; Oosting, M.; de Bree, L.C.J.; Koeken, V.A.C.M.; Moorlag, S.J.C.F.M.; Mourits, V.P.; van Diepen, J.; Strienstra, R.; Novakovic, B.; Stunnenberg, H.G.; van Crevel, R.; Joosten, L.A.B.; Netea, M.G.; Riksen, N.P. Rewiring of glucose metabolism defines trained immunity induced by oxidized low density lipoprotein. J. Mol. Med. (Berl.), 2020, 98(6), 819-831.
[http://dx.doi.org/10.1007/s00109-020-01915-w] [PMID: 32350546]
[29]
Quintin, J.; Saeed, S.; Martens, J.H.A.; Giamarellos-Bourboulis, E.J.; Ifrim, D.C.; Logie, C.; Jacobs, L.; Jansen, T.; Kullberg, B.J.; Wijmenga, C.; Joosten, L.A.B.; Xavier, R.J.; van der Meer, J.W.M.; Stunnenberg, H.G.; Netea, M.G. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe, 2012, 12(2), 223-232.
[http://dx.doi.org/10.1016/j.chom.2012.06.006] [PMID: 22901542]
[30]
Chavakis, T.; Mitroulis, I.; Hajishengallis, G. Hematopoietic progenitor cells as integrative hubs for adaptation to and fine-tuning of inflammation. Nat. Immunol., 2019, 20(7), 802-811.
[http://dx.doi.org/10.1038/s41590-019-0402-5] [PMID: 31213716]
[31]
Arts, R.J.; Joosten, L.A.; Netea, M.G. Immunometabolic circuits in trained immunity. Semin. Immunol., 2016, 28(5), 425-430.
[http://dx.doi.org/10.1016/j.smim.2016.09.002] [PMID: 27686054]

© 2024 Bentham Science Publishers | Privacy Policy