Abstract

Lactate used to be considered as a waste product of glucose metabolism. However, accumulating evidence has revealed its crucial role in regulating various biological and pathological processes. Hypoxia, inflammation, viral infection, and tumor promote the production of lactate. Then lactate activates G protein-coupled receptor 81 (GPR81) or shuttles across membranes by monocarboxylate-transporters (MCTs) to execute its intricate effects. Many studies highlighted the function of lactate in regulating dendritic cells, monocytes, natural killer cells, mast cells, T cells, tumor cells, fibroblasts, macrophages polarization, and the differentiation of Th1, Th17, MDSCs, Tregs; all of which play a role in maintaining the immune homeostasis of the host when challenged with the noxious stimuli. In this review, we summarized the influence of lactate in diverse tissue-specific cells, and discuss their effects on viral infection, acute inflammation, chronic inflammation, sepsis, and tumor immunosuppression. The goal of this review is to expose that lactate has a double-edged effect on host immunity and accompanying inflammatory reactions, which could be a potentially effective target for treating the tumor and multiple infectious diseases.

摘要

乳酸曾​​经被认为是葡萄糖代谢的废物。然而，越来越多的证据揭示了它在调节各种生物和病理过程中的关键作用。缺氧、炎症、病毒感染和肿瘤会促进乳酸的产生。然后乳酸激活 G 蛋白偶联受体 81 (GPR81) 或通过单羧酸转运蛋白 (MCT) 穿梭于细胞膜以执行其复杂的作用。许多研究强调了乳酸在调节树突细胞、单核细胞、自然杀伤细胞、肥大细胞、T细胞、肿瘤细胞、成纤维细胞、巨噬细胞极化以及Th1、Th17、MDSCs、Tregs分化中的作用；当受到有害刺激时，所有这些都在维持宿主的免疫稳态中发挥作用。在本次审查中，我们总结了乳酸对不同组织特异性细胞的影响，并讨论了它们对病毒感染、急性炎症、慢性炎症、败血症和肿瘤免疫抑制的影响。本综述的目的是揭示乳酸对宿主免疫和伴随的炎症反应具有双重作用，这可能是治疗肿瘤和多种传染病的潜在有效靶点。