OR11

1:University of Lübeck, University Medical Center Schleswig-Holstein, Campus Centrum Lübeck; 2:Research Center Borstel Leibniz Lung Center; 3:German Center of Lung Research (DZL); 4:German Center for Infection Research (DZIF)

Tuberculosis (TB), caused by Mycobacterium tuberculosis complex (MTBC) bacteria, remains a major global health challenge. MTBC has evolved diverse strategies to persist within the human host, including potential adaptation to specific human populations. One such strategy involves epigenetic reprogramming of host cells, particularly cells of the innate immune system. DNA methylation, a key epigenetic mechanism, has been shown to be altered in individuals with TB.

In this study, we investigate the epigenetic response to MTBC infection using an early-stage human macrophage infection model. We also examine long-term epigenetic changes in TB patients from a Gambian cohort. Specifically, we explore how MTBC lineages L4 and L6 influence DNA methylation and gene expression patterns in host cells. These findings are then correlated with DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) and clinical outcomes, including lung function.

By integrating in vitro and patient-derived data, we aim to identify lineage-specific host responses and epigenetic signatures associated with disease outcome. Our results can offer new insights into how MTBC modulates the host immune response through epigenetic mechanisms, advancing our understanding of TB pathophysiology and host-pathogen interactions.