Epigenetic programming of host lipid metabolism associated with resistance to TST/IGRA conversion after exposure to Mycobacterium tuberculosis

Tuberculosis (TB) remains an enduring global health challenge with millions of deaths and new cases each year. Despite recent advances in TB treatment, we lack an effective vaccine or a durable cure. While heavy exposure to Mycobacterium tuberculosis often results in latent TB latent infection (LTBI...

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Published inmSystems Vol. 9; no. 9; p. e0062824
Main Authors Dill-McFarland, Kimberly A., Simmons, Jason D., Peterson, Glenna J., Nguyen, Felicia K., Campo, Monica, Benchek, Penelope, Stein, Catherine M., Vaisar, Tomas, Mayanja-Kizza, Harriet, Boom, W. Henry, Hawn, Thomas R.
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 17.09.2024
Subjects
Adult
chromatin remodeling
Cohort Studies
DNA Methylation
Epigenesis, Genetic
Female
Genomics and Proteomics
Humans
Interferon-gamma Release Tests
interferons
Latent Tuberculosis - genetics
Latent Tuberculosis - immunology
Latent Tuberculosis - metabolism
Latent Tuberculosis - microbiology
Lipid Metabolism - genetics
Male
monocytes
Monocytes - immunology
Monocytes - metabolism
Mycobacterium tuberculosis
Research Article
Tuberculin Test
Uganda - epidemiology
Uganda
DNA methylation
chromatin remodeling
monocytes
interferons
Mycobacterium tuberculosis
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Summary:Tuberculosis (TB) remains an enduring global health challenge with millions of deaths and new cases each year. Despite recent advances in TB treatment, we lack an effective vaccine or a durable cure. While heavy exposure to Mycobacterium tuberculosis often results in latent TB latent infection (LTBI), subpopulations exist that are either resistant to infection or contain Mtb with interferon-gamma (IFNγ)-independent mechanisms not indicative of LTBI. These resisters provide an opportunity to investigate the mechanisms of TB disease and discover novel therapeutic targets. Here, we compare monocyte epigenetic profiles of RSTR and LTBI from a Ugandan household contact cohort. We identify methylation signatures in host lipid and cholesterol pathways with potential relevance to early TB clearance before the sustained IFN responses indicative of LTBI. This adds to a growing body of literature linking TB disease outcomes to host lipids.
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Present address: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
The authors declare no conflict of interest.
ISSN:2379-5077
2379-5077
DOI:10.1128/msystems.00628-24