DNA methylomes derived from alveolar macrophages display distinct patterns in latent tuberculosis - implication for interferon gamma release assay status determination

Host innate immune cells, including alveolar macrophages, have been identified as key players in the early eradication of Mycobacterium tuberculosis and in the maintenance of an anti-mycobacterial immune memory, which is believed to be induced through epigenetic changes. The aim of the study was to elucidate whether exposure to M. tuberculosis induced a different DNA methylation pattern of alveolar macrophages and pulmonary T lymphocytes. Alveolar macrophages and T lymphocytes were isolated from induced sputum obtained from individuals living in Lima, which is an area high endemic for tuberculosis. To determine the latent tuberculosis infection status of the subjects, an interferon-{gamma} release assay was performed. We evaluated the DNA methylomes of the alveolar macrophages and T lymphocytes using the Illumina Infinium Human Methylation 450K Bead Chip array, revealing a distinct DNA methylation pattern in alveolar macrophages allowing the discrimination of asymptomatic individuals with latent tuberculosis infection from non-infected individuals. Pathway analysis revealed that cell signalling of inflammation and chemokines in alveolar macrophages play a role in latent tuberculosis infection. In conclusion, we demonstrated that DNA methylation in alveolar macrophages can be used to determine the tuberculosis infection status of individuals in a high endemic setting.