DNA methylomes derived from alveolar macrophages and alveolar T cells display distinct patterns in tuberculosis – a future precision tool for TB status determination?

Abstract Background Host innate immune cells have been identified as key players in the early eradication of Mycobacterium tuberculosis and in the maintenance of an anti-mycobacterial immune memory, which we and others have shown are induced through epigenetic reprogramming. Studies on human tuberculosis immunity are dominated by those using peripheral blood as surrogate markers for immunity. We aimed to investigate DNA methylation patterns in immune cells of the lung compartment by obtaining induced sputum from patients with tuberculosis and subjects exposed to M. tuberculosis . Alveolar macrophages and alveolar T cells were isolated from the collected sputum and DNA methylome analyses performed (Illumina Infinium Human Methylation 450k). Results Multidimensional scaling analysis revealed that DNA methylomes of cells from the patients with tuberculosis, the exposed subjects and controls appeared as separate clusters. The numerous genes that were differentially methylated between the three groups were functionally connected and overlapped with previous findings of trained immunity and tuberculosis. In addition, analysis of the interferon-gamma release assay (IGRA) status of the subjects demonstrated that the IGRA status was reflected in the DNA methylome by a unique signature. Conclusions M. tuberculosis induces epigenetic reprogramming in immune cells, reflected as a specific DNA methylation pattern of immune cells in the lung compartment upon exposure to tuberculosis. The data of this pilot study suggests that DNA methylation-based biosignatures could be considered for further development towards a clinically useful tool for determining tuberculosis infection status and the level of tuberculosis exposure.