A differential DNA methylome signature of pulmonary immune cells from individuals converting to latent tuberculosis infection

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, spreads via aerosols and the first encounter with the immune system is with the pulmonary-resident immune cells. The role of epigenetic regulations in the immune cells is emerging and we have previously shown that macrophages capacity to kill M. tuberculosis is reflected in the DNA methylome. The aim of this study was to investigate epigenetic modifications in alveolar macrophages and T cells in a cohort of medical students with an increased risk of TB exposure, longitudinally. DNA methylome analysis revealed that a unique DNA methylation profile was present in healthy subjects who later developed latent TB during the study. The profile was reflected in a different overall DNA methylation distribution as well as a distinct set of differentially methylated genes (DMGs). The DMGs were over-represented in pathways related to metabolic reprogramming of macrophages and T cell migration and IFN-γ production, pathways previously reported important in TB control. In conclusion, we identified a unique DNA methylation signature in individuals, with no peripheral immune response to M. tuberculosis antigen who later developed latent TB. Together the study suggests that the DNA methylation status of pulmonary immune cells can reveal who will develop latent TB infection.

Relationship between DNA Methylation Profiles and Active Tuberculosis Development from Latent Infection: a Pilot Study in Nested Case-Control Design

“…The infection status of such controls was unknown. As has been reported by a longitudinal study which found healthy subjects who later developed LTBI had a unique DNA methylation profile ( 23 ), the aberrant DNA-methylated genes detected in aforementioned studied might confounded by LTBI status of the controls because of the complex immune progress from TB infection to active disease. Esterhuyse et al ( 24 ) incorporated dmCpGs from only monocytes and granulocytes by machine learning to distinguish active TB from LTBI in cross-sectional design and obtained a model with an AUC of 0.74, which was consistent with our results.…”

Cognitive dysfunction in post‐COVID‐19 condition: Mechanisms, management, and rehabilitation

“…There is growing evidence to suggest that viral and bacterial infections can lead to epigenetic changes in the host, which can affect the host's immune response and the severity of the infection [121][122][123]. Epigenetic changes refer to alterations in the way genes are expressed rather than changes in the underlying DNA sequence itself [124].…”

Macrophage memory: Types, mechanisms, and its role in health and disease

“…Indeed, a global methylation analysis showed that there existed over 1000 differentially methylated regions between PBMCs of tuberculosis (TB) patients and healthy controls, and there were still almost 4000 differentially methylated regions following completion of anti-TB treatment, and the majority of the affected genes were associated with the autophagy pathway [37,38]. Similarly, a distinct DNA methylation profile, which was enriched in the pentose phosphate pathway, T cell migration and IFN-γ production pathways, was uncovered in alveolar macrophages (AMs) after M. tuberculosis infection [39]. Intriguingly, there were more differentially methylated regions in AMs than in PMBCs within the same individual [38].…”