Compromised Metabolic Reprogramming Is an Early Indicator of CD8⁺ T Cell Dysfunction during Chronic Mycobacterium tuberculosis Infection.

ABSTRACT: The immunometabolic mechanisms underlying suboptimal T cell immunity in tuberculosis remain undefined. Here, we examine how chronic Mycobacterium tuberculosis (Mtb) and M. bovis BCG infections rewire metabolic circuits and alter effector functions in lung CD8⁺ T cells. As Mtb infection progresses, mitochondrial metabolism deteriorates in CD8⁺ T cells, resulting in an increased dependency on glycolysis that potentiates inflammatory cytokine production. Over time, these cells develop bioenergetic deficiencies that reflect metabolic "quiescence." This bioenergetic signature coincides with increased mitochondrial dysfunction and inhibitory receptor expression and was not observed in BCG infection. Remarkably, the Mtb-triggered decline in T cell bioenergetics can be reinvi

SUBMITTER: Russell SL 

PROVIDER: S-EPMC6915325 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature