Department of Biomedical Sciences, James H Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
Front Immunol. 2024 Sep 20;15:1483400. doi: 10.3389/fimmu.2024.1483400. eCollection 2024.
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.
乳酸在脓毒症和感染性休克中显著影响免疫细胞功能，超越了其作为代谢副产物的传统观念。本综述总结了乳酸作为生物标志物的作用及其对免疫细胞动力学的影响，强调了其在调节脓毒症期间免疫反应中的关键作用。从机制上讲，关键的乳酸转运蛋白如 MCT1、MCT4 和受体 GPR81 在介导这些效应中起着至关重要的作用。HIF-1α 也在乳酸驱动的免疫调节中发挥重要作用。此外，乳酸通过翻译后修饰如乳酰化、乙酰化和磷酸化来影响免疫细胞功能，这些修饰改变了酶活性和蛋白质功能。乳酸与免疫细胞之间的这些相互作用是理解与脓毒症相关的免疫失调的核心，为指导未来的研究和改善治疗策略以提高患者的预后提供了见解。
