期刊
FEBS JOURNAL
卷 289, 期 4, 页码 955-964出版社
WILEY
DOI: 10.1111/febs.15807
关键词
COVID-19; IDO; immunometabolism; kynurenine; NAD; niacin; SARS-CoV-2; tryptophan; vitamin B3; Warburg
资金
- Strategic Health Innovations Partnerships Unit of the South African Medical Research Council
- South African Department of Science and Technology
During infection, macrophages undergo divergent pathways of metabolism and switch between oxidative phosphorylation and aerobic glycolysis, with potential therapeutic implications for infectious diseases like sepsis and COVID-19. Manipulation of nicotinamide pathways could correct deleterious immune responses.
Divergent pathways of macrophage metabolism occur during infection, notably switching between oxidative phosphorylation and aerobic glycolysis (Warburg-like metabolism). Concurrently, macrophages shift between alternate and classical activation. A key enzyme upregulated in alternatively activated macrophages is indoleamine 2,3-dioxygenase, which converts tryptophan to kynurenine for de novo synthesis of nicotinamide. Nicotinamide can be used to replenish cellular NAD(+) supplies. We hypothesize that an insufficient cellular NAD(+) supply is the root cause of metabolic shifts in macrophages. We assert that manipulation of nicotinamide pathways may correct deleterious immune responses. We propose evaluation of nicotinamide (Vitamin B3) and analogues, including isoniazid, nicotinamide mononucleotide and nicotinamide riboside, as potential therapy for infectious causes of sepsis, including COVID-19.
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