Peripheral blood cellular dynamics during the progression of human tuberculosis

Tuberculosis (TB) remains a major global health challenge. Peripheral blood immune cell composition provides valuable insights into TB progression and management. In this study, we analyzed cellular dynamics across the TB disease spectrum using 43 global transcriptomic datasets encompassing 5,902 blood samples. Distinct immune changes were identified during the early stages of TB progression. Transition from latent infection to incipient TB was associated with reduced proportions of natural killer (NK) cells. In subclinical TB, monocyte proportions increased further, accompanied by additional reductions in NK cells and B cells. These early immune shifts preceded the pronounced alterations observed in active TB, characterized by elevated monocytes and neutrophils alongside markedly decreased lymphocyte populations. During successful anti-TB treatment, immune profiles gradually normalized. Cellular dynamics were also influenced by TB burden, age, and HIV coinfection, with stronger immune responses observed in adults and in regions with lower TB burdens. Overall, this study highlights early-stage peripheral blood biomarkers, particularly NK cell changes, as potential indicators of TB progression and targets for preventive interventions.