SMOKING-INDUCED GENETIC DRIVERS OF LATENT TUBERCULOSIS REACTIVATION UNVEILED BY SINGLE-CELL RNA SEQUENCING ANALYSIS

Abstract

Tuberculosis (TB), a formidable infectious disease caused by Mycobacterium tuberculosis, remains a significant global health challenge. While many individuals harbor a latent form of the infection, certain risk factors, such as cigarette smoking, can result in the reactivation of latent tuberculosis into an active and transmissible state. This phenomenon underscores the critical need to elucidate the molecular mechanisms by which smoking modulates the host immune response, rendering individuals more susceptible to tuberculosis reactivation. Single-cell RNA sequencing (scRNA-seq) was employed to comprehensively profile the transcriptomic landscape of immune cells from individuals with active tuberculosis, including a subset of smokers. By leveraging cutting-edge computational approaches, we identified distinct gene expression signatures and cellular subpopulations that were differentially expressed in smokers compared to non-smokers. Through rigorous bioinformatic analyses, key genes and pathways were uncovered associated with smoking-induced dysregulation of inflammatory responses and immune cell function, providing mechanistic insights into their heightened susceptibility to tuberculosis reactivation. Our findings pinpoint potential therapeutic targets and biomarkers for early detection and personalized management of tuberculosis, particularly in the context of smoking related risk.