COVID-19 Review Volume 12, Issue 24 pp 26263—26278
Immunometabolism at the cornerstone of inflammaging, immunosenescence, and autoimmunity in COVID-19
- 1 Vascular Medicine Department, CHU Rennes, French National Health and Medical Research (Inserm), Clinical Investigation Center (CIC) 1414, University of Rennes 1, Rennes F-35033, France
- 2 NuMeCan Institute, Exogenous and Endogenous Stress and Pathological Responses in Hepato-Gastrointestinal Diseases (EXPRES) Team, French National Health and Medical Research (Inserm) U1241, University of Rennes 1, Rennes F-35033, France
- 3 Cellular and Molecular Biology Consultant, Rennes F-35033, France
- 4 University of Reunion Island, INSERM, UMR 1188 Reunion, Indian Ocean Diabetic Atherothrombosis Therapies (DéTROI), CHU de La Réunion, Saint-Denis de La Réunion F-97400, France
- 5 AP-HP Hôpital Avicenne, Oncologie Médicale, Bobigny F-93000, France
- 6 Sorbonne University Paris Nord, INSERM, U942, Cardiovascular Markers in Stressed Conditions, MASCOT, Bobigny F-93000, France
- 7 Department of Pathology, Paris Diderot University, Sorbonne Paris Cité, Paris F-75010, France
Received: October 29, 2020 Accepted: December 10, 2020 Published: December 27, 2020
https://doi.org/10.18632/aging.202422How to Cite
Abstract
Inflammaging constitutes the common factor for comorbidities predisposing to severe COVID-19. Inflammaging leads to T-cell senescence, and immunosenescence is linked to autoimmune manifestations in COVID-19. As in SLE, metabolic dysregulation occurs in T-cells. Targeting this T-cell dysfunction opens the field for new therapeutic strategies to prevent severe COVID-19. Immunometabolism-mediated approaches such as rapamycin, metformin and dimethyl fumarate, may optimize COVID-19 treatment of the elderly and patients at risk for severe disease.
Abbreviations
ACE: angiotensin converting enzyme; AMPK: Adenosine monophosphate-activated protein kinase; ANK-1: Ankyrin 1; ARDS: Acute respiratory distress syndrome; ARE: antioxidant response elements; ATP: Adenosine triphosphate; BMI: Body mass index; CD: Cluster of differentiation; CMV: Cytomegalovirus; COVID-19: Coronavirus disease 2019; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4; CXCL: chemokine (C-X-C motif) ligand; DCs: Dendritic cells; DMF: Dimethyl fumarate; DNA: Deoxyribonucleic acid; EMRA: Effector memory CD45RA+; FAO: Fatty acid oxidation; G-CSF: Granulocyte Colony Stimulating factor; H2O2: Hydrogen peroxide; HIV: human immunodeficiency viruses; HO-1: heme oxygenase-1; HUVECs: Human umbilical vein endothelial Cells; ICU: Intensive care unit; IFN-γ: Interferon gamma; IL: Interleukin; IP-10: Interferon gamma-induced Protein 10; IRFs: interferon regulatory factors; JAK/STAT: Janus kinases/signal transducers and activators of transcription; JNK: Jun N-terminal kinase; Keap1: Kelch-like ECH-associated protein 1; MAVS: mitochondrial antiviral-signaling; MCP-1: Monocyte chemoattractant protein 1; MDA-5: Melanoma differentiation-associated protein 5; MHC: Major histocompatibility complex; MICA: MHC Class I polypeptide-related sequence A; MIP-1α: Macrophage inflammatory protein-1 alpha; mTOR: Mechanistic mammalian target of rapamycin; mTORC: mTOR complex; NADPH: Nicotinamide adenine dinucleotide phosphate; NET: Neutrophil extracellular traps; NF-κB: Nuclear factor-kappa B; NLRP3: NOD-like receptor family, pyrin domain containing 3; NOD: Non-obese diabetic; NQO1: NADPH quinone oxidoreductase 1; Nrf2: Nuclear factor E2-related factor 2; OH•: hydroxyl radical; OXPHOS: Oxidative phosphorylation; PD-L1: Programmed death-ligand 1; PI3K: Phosphoinositide 3-kinase; preBötC: Pre-Bötzinger complex; RA: Rheumatoid arthritis; RIG: Retinoic acid-inducible gene; RNA: Ribonucleic acid; ROS: Reactive oxygen species; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; SASP: Senescence associated secretory phenotype; SLE: Systemic lupus erythematosus; STING: Stimulator of interferon genes; TCR: T-cell receptor; TH: T helper cell; TGF-β: Transforming growth factor beta; TIGIT: T-cell immunoreceptor with Ig and ITIM (immunoreceptor tyrosine-based inhibition motif) domains; Tim-3: T-cell immunoglobulin mucin-3; TNF-α: Tumor necrosis factor alpha; Treg: Regulatory T-cell; VCAM-1: Vascular cell adhesion protein 1.