ArticleFrontiers in immunology2021
Extracellular Lactate Acts as a Metabolic Checkpoint and Shapes Monocyte Function Time Dependently.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 13 citations in OpenAlex.
- A Role for Astrocyte Metabolism in Species-Specific Neuronal Development.bioRxiv : the preprint server for biology · 2026Article
- Metabolic reprogramming of myeloid cells in cancer: from lactate-NAMPT axis to AI-guided therapeutics.Experimental & molecular medicine · 2026Review
- Hexokinase 3 promoted cytokine production of monocytes by targeting metabolic reprogramming and histone lactylation in sepsis.Clinical epigenetics · 2026Article
- Predicting extubation failure in patients with cardiorespiratory decompensation: development and validation of an interpretable machine learning-based risk calculator.Frontiers in cardiovascular medicine · 2026Article
- Linear dose-response relationship between vancomycin trough concentration and acute kidney injury in sepsis: effect modification by hyperlactatemia.Frontiers in pharmacology · 2026Article
- Eno1 in sepsis-induced coagulopathy: a pleiotropic mechanism hypothesis involving immunomodulation and endothelial dysfunction.Thrombosis journal · 2025Article
- Engineering immunity using metabolically active polymeric nanoparticles.Trends in biotechnology · 2025Review
- Monocyte CCL2 signaling possibly contributes to increased asthma susceptibility in type 2 diabetes.Scientific reports · 2025Article
- Article
- Staphylococci planktonic and biofilm environments differentially affect osteoclast formation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Metabolic Reprogramming and Its Regulatory Mechanism in Sepsis-Mediated Inflammation.Journal of inflammation research · 2023Review
- Understanding the Contribution of Lactate Metabolism in Cancer Progress: A Perspective from Isomers.Cancers · 2022Review
- Systematic Investigations on the Metabolic and Transcriptomic Regulation of Lactate in the Human Colon Epithelial Cells.International journal of molecular sciences · 2022Article
- Metabolic Reprogramming Mediates Delayed Apoptosis of Human Neutrophils Infected WithFrontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elevated blood lactate levels are frequently found in critically ill patients and thought to result from tissue hypoperfusion and cellular oxygen shortage. Considering the close relationship between immune cell function and intracellular metabolism, lactate is more than a glycolytic waste molecule but able to regulate the immune response. Our aim was to elucidate the temporal and mechanistic effect of extracellular lactate on monocytes. To this end, primary human monocytes and the human monocytic cell line MonoMac6 were stimulated with various toll-like-receptor agonists after priming with Na-L-lactate under constant pH conditions. As readout, cytokine production was measured, real-time assessment of intracellular energy pathways was performed, and intracellular metabolite concentrations were determined. Irrespective of the immunogenic stimulus, short-term Na-lactate-priming strongly reduced cytokine production capacity. Lactate and hexoses accumulated intracellularly and, together with a decreased glycolytic flux, indicate a lactate-triggered impairment of glycolysis. To counteract intracellular hyperglycemia, glucose is shunted into the branching polyol pathway, leading to sorbitol accumulation. In contrast, long-term priming with Na-L-lactate induced cellular adaption and abolished the suppressive effect. This lactate tolerance is characterized by a decreased cellular respiration due to a reduced complex-I activity. Our results indicate that exogenous lactate shapes monocyte function by altering the intracellular energy metabolism and acts as a metabolic checkpoint of monocyte activation.
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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.