Abstract
Several studies have identified biomarkers for tuberculosis (TB) diagnosis based on blood cell transcriptomics. Here, we instead studied epigenomics in the lung compartment by obtaining induced sputum from subjects included in a TB contact tracing. CD3- and HLA-DR-positive cells were isolated from the collected sputum and DNA methylome analyses performed. Unsupervised cluster analysis revealed that DNA methylomes of cells from TB-exposed individuals and controls appeared as separate clusters and the numerous genes that were differentially methylated were functionally connected. The enriched pathways were strongly correlated to data from published work on protective heterologous immunity to TB. Taken together, our results demonstrate that epigenetic changes related to trained immunity occurs in the pulmonary immune cells of TB-exposed individuals and that a DNA methylation signature can be derived from the DNA methylome. Such a signature can be further developed for clinical use as a marker of TB exposure.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This study was funded through generous grants from Forskningsradet Sydostra Sverige (FORSS-932096), the Swedish Research Council (2015-02593 and 2018-02961) and the Swedish Heart Lung Foundation (20150709 and 20180613). J.D is a postdoctoral fellow supported through the Medical Infection and Inflammation Center (MIIC) at Linkoping University.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The included subjects gave oral and written informed consent (ethical approval obtained from the regional ethical review board in Linkoping, #2016/237-31). The study protocol included questionnaires on respiratory and overall health, the evaluation of IGRA-status and sputum samples for DNA extraction.
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
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Data Availability
Sequencing datasets will be made publicly available upon acceptance and prior to final publication.