ArticleScience (New York, N.Y.)2014
mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity.
Article in Science (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04348370 (Bacillus Calmette-Guerin Vaccination as Defense Against SARS-CoV-2), which is not on this map. Cited by 1,366 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Bacillus Calmette-Guerin Vaccination as Defense Against SARS-CoV-2: A Randomized Controlled Trial to Protect Health Care Workers by Enhanced Trained Immune Responses
Who cites it
1,366 citing papers in PubMed, 1 synthesis or guideline pooled it, 2,074 citations in OpenAlex.
- Trained immunity in inflammatory bone disease: a bibliometric and literature-level text-mining analysis.Frontiers in immunology · 2026Pooled it
- Gut microbiota and immunometabolism in obesity.Gut microbes · 2026Review
- Trained Immunity in Childhood Vaccination.Acta paediatrica (Oslo, Norway : 1992) · 2026Review
- The epigenetic-metabolic axis of trained immunity: dual roles in disease pathogenesis and intervention.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Trained immunity in chronic, relapsing and low-grade joint inflammation.Nature reviews. Rheumatology · 2026Review
- Dynamic metabolic programming of monocyte-derived cells defines immunity in CNS disease.Brain : a journal of neurology · 2026Review
- Spatiotemporal heterogeneity and dynamic evolution of microglial glucose metabolic reprogramming in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Maturation-Dependent Constraints in the Ability of Human Monocytes to Initiate Trained Immunity.MedComm · 2026Article
- Research progress on lactate metabolism in lung cancer: Tumorigenesis, drug resistance and clinical translation (Review).Oncology reports · 2026Review
- Alveolar Macrophages: Development, Respiratory Homeostasis, Signal Pathways, Diseases, and Therapeutic Opportunities.MedComm · 2026Review
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Trained Immunity as a Mechanistic Bridge Between Uremic Toxins, Atherosclerosis, and Vascular Calcification in Chronic Kidney Disease.Cardiovascular toxicology · 2026Review
- Review
- Peripheral immune-cell bioenergetics in acute and stable schizophrenia.European archives of psychiatry and clinical neuroscience · 2026Article
- Drugging trained immunity: immunometabolic and epigenetic control of maladaptive inflammatory memory in chronic inflammatory diseases.Immunologic research · 2026Review
- Article
- The Metabolic Reprogramming Mechanism of Astragalus Polysaccharide-Induced Immune Memory in HD11 Cells: Integrated Analysis Based on Glycolysis and the TLR2/mTOR Pathway.Poultry science · 2026Article
- Molecular Mechanisms and Therapeutic Targeting of the Macrophage Metabolic-Epigenetic Interaction Network in Chronic Obstructive Pulmonary Disease.Cell biochemistry and biophysics · 2026Review
- Immune regulation by erythroid cells: how erythroid progenitor cells and mature red blood cells shape immunity.Nature reviews. Immunology · 2026Review
- Chronic infection and metabolic stress: a converging axis driving hypertension and metabolic dysfunction-associated steatotic liver disease outcomes.American journal of hypertension · 2026Review
1,306 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issuedvan der Meer, Brian M J W [corrected to van der Veer, Brian M J W]
Authors and funding
28 authors at 9 institutions in 3 countries.
Funding
Abstract
Epigenetic reprogramming of myeloid cells, also known as trained immunity, confers nonspecific protection from secondary infections. Using histone modification profiles of human monocytes trained with the Candida albicans cell wall constituent β-glucan, together with a genome-wide transcriptome, we identified the induced expression of genes involved in glucose metabolism. Trained monocytes display high glucose consumption, high lactate production, and a high ratio of nicotinamide adenine dinucleotide (NAD(+)) to its reduced form (NADH), reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin (mTOR) through a dectin-1-Akt-HIF-1α (hypoxia-inducible factor-1α) pathway. Inhibition of Akt, mTOR, or HIF-1α blocked monocyte induction of trained immunity, whereas the adenosine monophosphate-activated protein kinase activator metformin inhibited the innate immune response to fungal infection. Mice with a myeloid cell-specific defect in HIF-1α were unable to mount trained immunity against bacterial sepsis. Our results indicate that induction of aerobic glycolysis through an Akt-mTOR-HIF-1α pathway represents the metabolic basis of trained immunity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.