Hyperglycemic Milieu Impairs Vγ9Vδ2 T Cell Functions in Tuberculosis Patients and Prolongs M.tb Negative Conversion Time

γδ T cells play protective roles in tuberculosis (TB). Our work demonstrated the therapeutic potential of allogeneic Vγ9Vδ2 T cells in TB patients. However, their functions in TB require further comprehensive evaluation. Here, we compared γδ T cells in TB patients and healthy adults at the bulk and single-cell RNA and protein levels, revealing that impaired glucose metabolism critically undermines their anti-infective functions. Excessive glucose disrupts γδ T cell effector functions, correlating with prolonged sputum smear conversion time in TB patients with type II diabetes. Additionally, serum glucose levels were linked to multidrug-resistant TB. These findings suggest that weakened Vδ2+γδ T cell responses in diabetic TB patients contribute to multidrug resistance. Restoring Vδ2+γδ T cell function offers a promising strategy for TB treatment. [Display omitted] •Reduced Vδ2+CD3 T cells mark peripheral γδ T cell imbalance in TB patients.•Glucose metabolism dysregulation impairs γδ T cells’ anti-infection function in TB.•Excessive glucose suppresses the CD107a expression of Vδ2+γδ T cells.•Hyperglycemia links to γδ T cell dysfunction, MDR-TB emergence, and poor prognosis.