Mucosal-associated invariant T (MAIT) cells are functionally impaired and metabolically altered in patients with chronic HBV infection

Chronic infection with hepatitis B virus (CHB) affects more than 250 million people worldwide and represents a major global health burden. In CHB patients, conventional virus-specific CD8+T cells are rendered dysfunctional. In contrast, the functionality of mucosal-associated invariant T (MAIT) cells, innate like T cells enriched in the liver, in CHB remains unclear. Here, we investigate the functionality and metabolic regulation of MAIT cells in patients with CHB.

MAIT cells were isolated from peripheral blood of CHB patients with or without nucleos(t)ide analogue (NUC) treatment or controls. Phenotype, functionality and metabolic features of MAIT cells were analysed by multi-colour flow cytometry.

MAIT cells were detected in similar frequencies in patients with CHB and healthy controls. Phenotypic analysis demonstrated an activated phenotype of MAIT cells in CHB patients with and without NUC treatment. However, following ex vivo re-stimulation, MAIT cells from CHB patients without NUC treatment expressed lower levels of effector molecules, such as Granzyme B and IFN□□ compared to MAIT cells from NUC-treated CHB patients. Metabolic analyses revealed defects in glucose uptake and higher mitochondrial mass in MAIT cells from CHB patients compared to controls. While effector cytokine expression by MAIT cells of controls required glycolysis, expression of granzyme B and TNF by CHB MAIT cells was independent of glycolysis.

Our data demonstrate functional and metabolic alterations of MAIT cells in CHB patients that may be targeted to improve therapeutic strategies against HBV.

Publication History

Article published online:
20 January 2025