Peripheral blood cellular dynamics during the progression of human tuberculosis

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health challenge. The composition of peripheral blood immune cells offers valuable insights into the progression and management of TB. In this study, we analyzed cellular dynamics across the TB disease spectrum using 43 global transcriptomic datasets encompassing 5,902 blood samples. Our findings reveal distinct immune changes during the early stages of TB progression. As latent TB infection (LTBI) transitions to incipient TB (ITB), monocyte proportions increase, while natural killer (NK) cell counts decline. In subclinical TB (STB), monocyte levels rise further, alongside reductions in NK cells and B cells. These early immune shifts precede the pronounced alterations observed in active TB (ATB), where elevated monocytes and neutrophils are accompanied by significant decrease in lymphocyte populations, including CD4+ and CD8+ T cells, B cells, and NK cells. During successful anti-TB treatment (ATT), immune profiles gradually normalize, characterized by reductions in monocytes and neutrophils and increases in lymphocyte populations. Factors such as TB burden, age, and HIV co-infection influence these cellular dynamics, with adults and individuals in low TB burden regions exhibiting more pronounced immune responses. This study implies the potential of early-stage peripheral blood biomarkers, such as NK cell changes, for detecting TB progression and facilitating targeted preventive interventions. Additionally, it emphasizes the importance of diverse datasets in improving the reliability of discoveries and advancing TB diagnostics and treatment strategies.