Lactate cross-talk in host-pathogen interactions

Alba Llibre, Frances S Grudzinska, Matthew K O'Shea, Darragh Duffy, David R Thickett, Claudio Mauro, Aaron Scott

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Abstract

Lactate is the main product generated at the end of anaerobic glycolysis or during the Warburg effect and its role as an active signalling molecule is increasingly recognised. Lactate can be released and used by host cells, by pathogens and commensal organisms, thus being essential for the homeostasis of host-microbe interactions. Infection can alter this intricate balance, and the presence of lactate transporters in most human cells including immune cells, as well as in a variety of pathogens (including bacteria, fungi and complex parasites) demonstrates the importance of this metabolite in regulating host-pathogen interactions. This review will cover lactate secretion and sensing in humans and microbes, and will discuss the existing evidence supporting a role for lactate in pathogen growth and persistence, together with lactate's ability to impact the orchestration of effective immune responses. The ubiquitous presence of lactate in the context of infection and the ability of both host cells and pathogens to sense and respond to it, makes manipulation of lactate a potential novel therapeutic strategy. Here, we will discuss the preliminary research that has been carried out in the context of cancer, autoimmunity and inflammation.

Original languageEnglish
Pages (from-to)3157-3178
Number of pages22
JournalThe Biochemical journal
Volume478
Issue number17
DOIs
Publication statusPublished - 7 Sept 2021

Bibliographical note

Funding Information:
A.L. is supported by the European Commission (H2020-MSCA-IF-2018, 841729). F.S.G. is supported by The Dunhill Medical Trust (RTF1906\86). D.R.T. and A.S. report funding from the British Lung Foundation (PPRG16-12), the Medical Research Council (MR/S002782/1) and the Health Technology Assessment (NIHR129593). C.M. is supported by the Medical Research Council (MR/T016736/1) and by a Professorial Fellowship and Translational Funds from the University of Birmingham.

Publisher Copyright:
© 2021 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

Keywords

  • host-pathogen interactions
  • immunometabolism
  • infection
  • lactate

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology

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