Immunometabolic Reprogramming of Monocytes in Tuberculosis Infection and Disease
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Rationale
Tuberculosis remains the leading cause of death from an infectious disease, caused by Mycobacterium tuberculosis . The term “latent tuberculosis infection” has been redefined as “tuberculosis infection,” reflecting immune recognition without clinical disease. Monocytes play a critical role in the innate immune response to Mycobacterium tuberculosis , both in the blood and in the lung, where they can repopulate the alveolar macrophage niche. However, it is unknown whether tuberculosis infection is associated with a distinct immunometabolic monocyte profile and how treatment impacts monocyte function.
Objectives
To define blood monocyte phenotype and metabolism in individuals with tuberculosis infection and tuberculosis disease, and to evaluate the impact of treatment on monocyte metabolic function.
Measurements
Circulating monocytes from individuals with tuberculosis infection, tuberculosis disease, and healthy controls were analysed ex vivo and following Mycobacterium tuberculosis stimulation. We assessed surface phenotype, cytokine and chemokine production, and metabolic activity. Groups were stratified based on treatment status.
Main Results
Monocytes from individuals with tuberculosis infection and tuberculosis disease were functionally similar to each other but distinct from healthy controls. Both groups exhibited reduced mitochondrial dependence, which was restored in people receiving treatment. Upon stimulation with Mycobacterium tuberculosis , only monocytes from individuals with tuberculosis infection demonstrated enhanced metabolic activity and reduced mitochondrial dependence, along with a unique functional profile.
Conclusions
Tuberculosis infection induces a distinct immunometabolic monocyte signature that may be reversible with treatment. These findings support the clinical relevance of tuberculosis infection and the potential for targeting monocytes through host-directed therapies.
