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

Pehrson, Isabelle; Mendez-Aranda, Melissa; Das, Jyotirmoy; Ugarte Gil, Cesar Augusto; Lerm, Maria; Idh, Nina; Paues, Jakob; Sayyab, Shumaila

dc.contributor.author	Pehrson, Isabelle
dc.contributor.author	Sayyab, Shumaila
dc.contributor.author	Das, Jyotirmoy
dc.contributor.author	Idh, Nina
dc.contributor.author	Paues, Jakob
dc.contributor.author	Mendez-Aranda, Melissa
dc.contributor.author	Ugarte Gil, Cesar Augusto
dc.contributor.author	Lerm, Maria
dc.date.accessioned	2023-01-06T13:40:11Z
dc.date.available	2023-01-06T13:40:11Z
dc.date.issued	2022
dc.identifier.uri	https://hdl.handle.net/20.500.12866/12988
dc.description.abstract	Background: Host 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). Results: Multidimensional 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. Conclusions: This 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.	en_US
dc.language.iso	eng
dc.publisher	BioMed Central
dc.relation.ispartofseries	Clinical Epigenetics
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.rights.uri	https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject	DNA methylation	en_US
dc.subject	Tuberculosis	en_US
dc.subject	Biosignature	en_US
dc.subject	Epigenetics	en_US
dc.subject	Sputum induction	en_US
dc.subject	IGRA	en_US
dc.title	The spectrum of tuberculosis described as differential DNA methylation patterns in alveolar macrophages and alveolar T cells	en_US
dc.type	info:eu-repo/semantics/article
dc.identifier.doi	https://doi.org/10.1186/s13148-022-01390-9
dc.type.version	info:eu-repo/semantics/publishedVersion
dc.relation.issn	1868-7083