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

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Karlsson L.
Das J.
Nilsson M.
Tyrén A.
Pehrson I.
Idh N.
Sayyab S.
Paues J.
Ugarte-Gil C.
Méndez-Aranda M.
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Nature Research
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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-? 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. © 2021, The Author(s).
We would like to show our appreciation to the medical personnel at Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, for assistance in sample collections and analysis of QuantiFERON® TB-Gold Plus test. We thank the Bioinformatics and Expression Analysis core facility (BEA) at Karolinska Institute that preformed the sequencing analysis. We thank the Swedish National Infrastructure for Computing (SNIC) at National Supercomputing Centre (NSC), Linköping University for the computing systems enabling the data handling, partially funded by the Swedish Research Council through grant agreement No. 2018-05973. The work was supported by grants from the Swedish Research Council No. 2018-04246 and the Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica CONCYTEC and Cienciactiva No. 106-2018-FONDECYT. J.D is a postdoctoral fellow supported through the Medical Infection and Inflammation Center (MIIC) at Linköping University.
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tuberculosis infection, epigenetic modifications