A bittersweet response to infection in diabetes ; targeting neutrophils to modify inflammation and improve host immunity
| Autor: | Ahmed Iqbal, Lynne R. Prince, Rebecca Dowey, Ian Sabroe, Simon R. Heller |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
endocrine system diseases Neutrophils type 1 diabetes Immunology Inflammation Disease Type 2 diabetes Review Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Immune system medicine Immunology and Allergy Humans Type 1 diabetes Innate immune system business.industry SARS-CoV-2 COVID-19 neutrophil NETosis Neutrophil extracellular traps RC581-607 medicine.disease infection 030104 developmental biology Diabetes Mellitus Type 1 Diabetes Mellitus Type 2 inflammation 030220 oncology & carcinogenesis type 2 diabetes medicine.symptom Immunologic diseases. Allergy business hyperglycaemia |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) |
| Popis: | Chronic and recurrent infections occur commonly in both type 1 and type 2 diabetes (T1D, T2D) and increase patient morbidity and mortality. Neutrophils are professional phagocytes of the innate immune system that are critical in pathogen handling. Neutrophil responses to infection are dysregulated in diabetes, predominantly mediated by persistent hyperglycaemia; the chief biochemical abnormality in T1D and T2D. Therapeutically enhancing host immunity in diabetes to improve infection resolution is an expanding area of research. Individuals with diabetes are also at an increased risk of severe coronavirus disease 2019 (COVID-19), highlighting the need for re-invigorated and urgent focus on this field. The aim of this review is to explore the breadth of previous literature investigating neutrophil function in both T1D and T2D, in order to understand the complex neutrophil phenotype present in this disease and also to focus on the development of new therapies to improve aberrant neutrophil function in diabetes. Existing literature illustrates a dual neutrophil dysfunction in diabetes. Key pathogen handling mechanisms of neutrophil recruitment, chemotaxis, phagocytosis and intracellular reactive oxygen species (ROS) production are decreased in diabetes, weakening the immune response to infection. However, pro-inflammatory neutrophil pathways, mainly neutrophil extracellular trap (NET) formation, extracellular ROS generation and pro-inflammatory cytokine generation, are significantly upregulated, causing damage to the host and perpetuating inflammation. Reducing these proinflammatory outputs therapeutically is emerging as a credible strategy to improve infection resolution in diabetes, and also more recently COVID-19. Future research needs to drive forward the exploration of novel treatments to improve infection resolution in T1D and T2D to improve patient morbidity and mortality. |
| Databáze: | OpenAIRE |
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