The spectrum of tuberculosis described as differential DNA methylation patterns in alveolar macrophages and alveolar T cells

Clinical Epigenetics

Research

Maria Lerm¹  Shumaila Sayyab¹  Nina Idh¹  Isabelle Pehrson¹  Jyotirmoy Das²  Jakob Paues³  Melissa Méndez-Aranda⁴  César Ugarte-Gil⁵ 

[1] Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Lab 1, Floor 12, 58185, Linköping, Sweden;Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Lab 1, Floor 12, 58185, Linköping, Sweden;Bioinformatics Unit (Core Facility), Linköping University, Linköping, Sweden;Clinical Genomics Linköping, SciLife Laboratory, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden;Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Lab 1, Floor 12, 58185, Linköping, Sweden;Division of Infectious Diseases, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden;Laboratorio de Investigación en Enfermedades Infecciosas, Facultad de Ciencias Y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru;School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru;Instituto de Medicina Tropical Alexander Von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru;

关键词: DNA methylation;    Tuberculosis;    Biosignature;    Epigenetics;    Sputum induction;    IGRA;   

DOI  :  10.1186/s13148-022-01390-9

 received in 2022-06-15, accepted in 2022-11-29,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundHost innate immune cells have been identified as key players in the early eradication of Mycobacterium tuberculosis and in the maintenance of an anti-mycobacterial immune memory, which we and others have shown are induced through epigenetic reprogramming. Studies on human tuberculosis immunity are dominated by those using peripheral blood as surrogate markers for immunity. We aimed to investigate DNA methylation patterns in immune cells of the lung compartment by obtaining induced sputum from M. tuberculosis- exposed subjects including symptom-free subjects testing positively and negatively for latent tuberculosis as well as patients diagnosed with active tuberculosis. Alveolar macrophages and alveolar T cells were isolated from the collected sputum and DNA methylome analyses performed (Illumina Infinium Human Methylation 450 k).ResultsMultidimensional scaling analysis revealed that DNA methylomes of cells from the tuberculosis-exposed subjects and controls appeared as separate clusters. The numerous genes that were differentially methylated between the groups were functionally connected and overlapped with previous findings of trained immunity and tuberculosis. In addition, analysis of the interferon-gamma release assay (IGRA) status of the subjects demonstrated that the IGRA status was reflected in the DNA methylome by a unique signature.ConclusionsThis pilot study suggests that M. tuberculosis induces epigenetic reprogramming in immune cells of the lung compartment, reflected as a specific DNA methylation pattern. The DNA methylation signature emerging from the comparison of IGRA-negative and IGRA-positive subjects revealed a spectrum of signature strength with the TB patients grouping together at one end of the spectrum, both in alveolar macrophages and T cells. DNA methylation-based biosignatures could be considered for further development towards a clinically useful tool for determining tuberculosis infection status and the level of tuberculosis exposure.

【 授权许可】

CC BY   
© The Author(s) 2022

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