ArticleRedox biology2021
Glutathione synthesis primes monocytes metabolic and epigenetic pathway for β-glucan-trained immunity.
Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Trained immunity induction by β-glucan under distinct immune training schemes in a mouse model.Immunologic research · 2026Article
- CHAC2-mediated glutathione metabolic reprogramming drives N1 polarization of bone marrow neutrophils and exacerbates inflammatory comorbidities.International journal of oral science · 2026Article
- Review
- Trained immunity modulators: A new frontier in immunoregulation and disease intervention.Journal of advanced research · 2026Review
- Slc7a11-Mediated Cystine/Glutamate Antiport Reprograms Macrophage Polarization and Ameliorates Atherosclerosis.MedComm · 2026Article
- Cuproptosis promotes inflammatory osteolysis via GYS1-mediated glycogen metabolism.International journal of oral science · 2026Article
- The pathogenicity and future treatment strategies ofFrontiers in cellular and infection microbiology · 2026Review
- A pathogen peptidoglycan scaffold coated with artificial biomembrane promotes broad resistance to bacterial infections by dynamically reprogramming macrophage metabolism.Materials today. Bio · 2025Article
- Aurora kinase A promotes trained immunity via regulation of endogenous S-adenosylmethionine metabolism.eLife · 2025Article
- Immunomodulatory activity of Pleurotus pulmonarius crude extract to human monocyte against Cryptococcus neoformans.BMC complementary medicine and therapies · 2025Article
- Redox-signaling in innate immune memory: Similar mechanisms in animals/humans and plants.Redox biology · 2025Review
- Lactate activates trained immunity by fueling the tricarboxylic acid cycle and regulating histone lactylation.Nature communications · 2025Article
- Systemic infection by Candida albicans requires FASN-α subunit induced cell wall remodeling to perturb immune response.PLoS pathogens · 2025Article
- Recent Advances of Trained immunity in Macrophages.International journal of biological sciences · 2025Review
- Critical Roles of the Cysteine-Glutathione Axis in the Production of γ-Glutamyl Peptides in the Nervous System.International journal of molecular sciences · 2023Review
- New insights into inflammatory memory of epidermal stem cells.Frontiers in immunology · 2023Review
- Article
- Trained immunity: A Yin-Yang balance.MedComm · 2022Review
- Noncoding RNAs in the Glycolysis of Ovarian Cancer.Frontiers in pharmacology · 2022Review
- Innate Immune Memory in Macrophages.Newborn (Clarksville, Md.)Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trained monocytes and macrophages produce reactive oxygen species (ROS), which trigger antioxidative glutathione (GSH) response to buffer the rising ROS. However, whether and how the trained immunity is shaped by GSH synthesis remains unknown. Here, we report that β-glucan-trained macrophages from mice harboring a myeloid-specific deletion of the catalytic subunit of glutamate-cysteine ligase (Gclc) showed impaired GSH synthesis and decreased proinflammatory cytokine production in response to lipopolysaccharide challenge. Gclc deficiency compromised the activation of mammalian target of rapamycin-1 (mTOR) and expression of c-Myc transcription factors, abrogating the energy utilization and the metabolic reprogramming that allows β-glucan-trained macrophages to switch to glycolysis and glutaminolysis. Furthermore, Gclc deletion repressed effective H3K27me3 demethylation in the promoters of immunometabolic genes, such as Gls, Hk2, and Glut1, in β-glucan-trained macrophages by promoting the methyltransferase enhancer of zeste homolog 2 (EZH2). In vivo, myeloid-specific ablation of Gclc decreased the secretion of proinflammatory cytokines upon rechallenge with Candida albicans and these animals were less protected against the infection, compared with control littermates. Moreover, pharmacological inhibition of EZH2 enhanced the trained immunity response against Candida infection in Gclc-deficient mouse and human peripheral blood mononuclear cells treated with GCLC inhibitor buthionine sulfoximine (BSO). Thus, antioxidative GSH synthesis supports an environment conducive to β-glucan-induced metabolic and epigenetic reprogramming in trained immunity, allowing exploration of its functional consequences in autoimmune or inflammatory disease.
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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.