Lactate cross-talk in host–pathogen interactions

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.

Interleukin-17 contributes to Ross River virus-induced arthritis and myositis

“…CD180 contributes to the homeostasis and survival of these cells, and promotes TLR4 signaling-mediated activation and proliferation of B cells, whilst inhibiting TLR4 signaling in macrophages and dendritic cells [ 107 – 109 ]. In the same group, SLC16A3, a lactate transporter expressed by macrophages and neutrophils, was also upregulated [ 110 , 111 ]. SLC16A3 is highly expressed by synovial fibroblasts (FLS) in RA synovial tissue, and silencing SLC16A3 inhibited the proliferation of RA-derived FLS and reduced disease severity in a RA mouse model [ 112 ].…”

Inhibition of SREBP-1 Activation by a Novel Small-Molecule Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Tissue to Radiofrequency Ablation

“…Human malignancies (especially HCC) are often characterized by anaerobic glycolysis/Warburg effect (47)(48)(49). These features aid energy generation for cellular proliferation and participate in alteration of the tumor microenvironment (49)(50)(51). Lipid metabolism is closely related to glucose metabolism (26).…”

Microbial lactate utilisation and the stability of the gut microbiome

“…In addition to impacting several important bacterial pathogens, lactate may also increase the virulence of the fungal pathogen Candida albicans , either by acting as a carbon source for growth, or by enhancing biofilm formation and resistance to antifungal compounds (Llibre et al, 2021). Exposure to lactate also triggers masking of key cell wall antigens by C. albicans , thereby making the pathogen less visible to the immune system (Ballou et al, 2016).…”