Diabetes and susceptibility to infections: Implication for COVID‐19. Issue 3 (24th June 2021)

• Record Type: Journal Article
• Authors: van Niekerk, Gustav; van der Merwe, Michelle; Engelbrecht, Anna‐Mart
• Is Part Of: Immunology. Volume 164:Issue 3(2021)
• Page Start: 467
• Page End: 475
• Publication Date: 2021-06-24
• Subjects: COVID‐19 -- diabetes -- immune checkpoint blocker -- inflammation -- insulin -- insulin resistance; Immunology -- Periodicals
• DOI: 10.1111/imm.13383
• Languages: English
• ISSNs: 0019-2805

Abstract

Abstract: A number of mechanisms have been proposed to explain the well‐established link between diabetic status and an increased susceptibility to infection. Notably, diabetes has been shown to be one of the strongest factors influencing healthcare outcome in COVID‐19 infections. Though it has long been noted that lymphocytes upregulate insulin receptors following immune activation, until recently, this observation has received little attention. Here, we point out key findings implicating dysregulated insulin signalling in immune cells as a possible contributing factor in the immune pathology associated with diabetes. Mechanistically, insulin, by activating the PI3K/Akt/mTOR pathway, regulates various aspects of both myeloid cells and lymphocytes, such as cell survival, metabolic reprogramming and the polarization and differentiation of immune cells. PI3K signalling is also supressed by immune checkpoint proteins, suggesting that insulin signalling may antagonize peripheral tolerance. Remarkably, it has also recently been shown that, following insulin binding, the insulin receptor translocates to the nucleus where it plays a key role in regulating the transcription of various immune‐related genes, including pathways involved in viral infections. Taken together, these observations suggest that dysregulated insulin signalling may directly contribute to a defective immune response during COVID‐19 infections. Abstract : Recent studies have shown that insulin signalling plays a key role in mediating immune cell functions such as driving metabolic reprogramming in activated immune cells. Insulin may also antagonize the anti‐inflammatory effect of immune checkpoint proteins and attenuate FOXO‐mediated anti‐inflammatory transcription in immune cells. Dysregulated insulin signalling in diabetes may thus contribute to the immune dysfunction that leads to increased susceptibility to various infections.