Effects of lactate in immunosuppression and inflammation: Progress and prospects

Int Rev Immunol. 2022;41(1):19-29. doi: 10.1080/08830185.2021.1974856. Epub 2021 Sep 6.

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.

Keywords: Acute inflammation; chronic inflammation; lactate/lactic acid; sepsis; tumor; virus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Immunosuppression Therapy
  • Inflammation
  • Lactic Acid* / metabolism
  • Neoplasms* / metabolism
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • Receptors, G-Protein-Coupled
  • Lactic Acid