Human MAIT cells show metabolic quiescence with rapid glucose-dependent upregulation of granzyme B upon stimulation.
Madeleine E ZinserAndrew J HightonAyako KuriokaBarbara KronsteinerJoachim HagelTianqi LengEmanuele MarchiChansavath PhetsouphanhChris B WillbergSusanna J DunachiePaul KlenermanPublished in: Immunology and cell biology (2018)
Mucosal-associated invariant T (MAIT) cells are a well-characterized innate-like T cell population abundant in the human liver, peripheral tissues and blood. MAIT cells serve in the first line of defense against infections, through engagement of their T cell receptor, which recognizes microbial metabolites presented on MR1, and through cytokine-mediated triggering. Typically, they show a quiescent memory phenotype but can undergo rapid upregulation of effector functions including cytolysis upon stimulation. T cells profoundly change their cellular metabolism during their maturation and activation. We sought to determine how MAIT cell metabolism may facilitate both the long-term memory phase in tissue and the transition to rapid effector function. Here, we show, by flow cytometric metabolism assays and extracellular flux analysis that, despite an effector-memory profile, human MAIT cells are metabolically quiescent in a resting state comparable to naïve and central memory T cells. Upon stimulation, they rapidly increase uptake of glucose and show a concomitant upregulation of the effector molecules notably granzyme B, which is impaired by inhibition of glycolysis with 2-deoxyglucose. These findings suggest that MAIT cells share some metabolic characteristics of both resting and effector T cell subsets, with a rapid transition upon triggering. Metabolic programming of this cell type may be of interest in understanding and modulating their function in infectious diseases and cancer.
Keyphrases
- induced apoptosis
- cell cycle arrest
- signaling pathway
- regulatory t cells
- resting state
- dendritic cells
- immune response
- endothelial cells
- working memory
- functional connectivity
- magnetic resonance imaging
- endoplasmic reticulum stress
- cell proliferation
- cell death
- social media
- ms ms
- metabolic syndrome
- high throughput
- adipose tissue
- skeletal muscle
- squamous cell carcinoma
- blood glucose
- weight loss
- induced pluripotent stem cells
- data analysis
- loop mediated isothermal amplification