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Frontiers in immunology
2024;15 1483400.

Lactate's impact on immune cells in sepsis: unraveling the complex interplay.

Tao Zhang, Linjian Chen, Gatkek Kueth, Emily Shao, Xiaohui Wang, Tuanzhu Ha, David L Williams, Chuanfu Li, Min Fan, Kun Yang
Author Information
  1. Tao Zhang: Department of Biomedical Sciences, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
  2. Linjian Chen: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
  3. Gatkek Kueth: James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
  4. Emily Shao: Program in Neuroscience, College of Arts and Science, Vanderbilt University, Nashville, TN, United States.
  5. Xiaohui Wang: Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
  6. Tuanzhu Ha: Department of Biomedical Sciences, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
  7. David L Williams: Department of Biomedical Sciences, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
  8. Chuanfu Li: Department of Biomedical Sciences, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
  9. Min Fan: Department of Biomedical Sciences, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
  10. Kun Yang: Department of Biomedical Sciences, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
PMID: 39372401 DOI: 10.3389/fimmu.2024.1483400

Abstract

Lactate significantly impacts immune cell function in sepsis and septic shock, transcending its traditional view as just a metabolic byproduct. This review summarizes the role of lactate as a biomarker and its influence on immune cell dynamics, emphasizing its critical role in modulating immune responses during sepsis. Mechanistically, key lactate transporters like MCT1, MCT4, and the receptor GPR81 are crucial in mediating these effects. HIF-1α also plays a significant role in lactate-driven immune modulation. Additionally, lactate affects immune cell function through post-translational modifications such as lactylation, acetylation, and phosphorylation, which alter enzyme activities and protein functions. These interactions between lactate and immune cells are central to understanding sepsis-associated immune dysregulation, offering insights that can guide future research and improve therapeutic strategies to enhance patient outcomes.

Keywords

immune cells immune response immunosuppression inflammation lactate lactic acid lactylation sepsis

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MeSH Term

Humans
Sepsis
Lactic Acid
Animals
Monocarboxylic Acid Transporters
Biomarkers
Receptors, G-Protein-Coupled
Hypoxia-Inducible Factor 1, alpha Subunit
Protein Processing, Post-Translational
Muscle Proteins
Symporters

Chemicals

Lactic Acid
Monocarboxylic Acid Transporters
Biomarkers
Receptors, G-Protein-Coupled
Hypoxia-Inducible Factor 1, alpha Subunit
monocarboxylate transport protein 1
HCAR1 protein, human
Muscle Proteins
Symporters
SLC16A4 protein, human
Journal Article Review

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