Journal Article

DZNE-2025-01254

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Deep immune profiling delineates hallmarks of disease heterogeneity in extrapulmonary tuberculosis.

Theobald, S. J. ; Dahm, K. (First author)DZNE* ; Lange, D. ; Spintge, J. S.DZNE* ; Winter, S. ; Klingmüller, A. ; Holsten, L.DZNE* ; Simonis, A. ; De Domenico, E.DZNE* ; Walczak, H. ; van Uelft, M.DZNE* ; Schultze, J. L.DZNE* ; Beyer, M. D.DZNE* ; Ulas, T. (Last author)DZNE* ; Suárez, I. ; Rybniker, J.

2025
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-025-65561-x

Abstract: Our understanding of the immune response in tuberculosis (TB) remains incomplete. This applies in particular to extrapulmonary TB (EPTB), a highly heterogeneous disease affecting up to 30% of patients in certain regions. Based on data-driven clustering of blood transcriptomes in an EPTB patient cohort, we define three highly distinct immunotypes. Combining bulk with single-cell RNA-sequencing delineates immunological trajectories characterized by dynamic IFN- and IL-1-mediated signalling in monocytes, alongside hyperactivation of T and NK cells, ultimately resulting in extensive immune dysregulation. Integrative analysis of multi-omics data provides deep insights into different layers of the anti-tuberculous immune response and the identification of immunotypes enabling stratification strategies for personalized host-directed treatments. In addition, our comprehensive approach helps to develop an accurate diagnostic gene expression signature for both EPTB and pulmonary TB highlighting the translational potential of our data.

Keyword(s): Humans (MeSH) ; Tuberculosis: immunology (MeSH) ; Tuberculosis: genetics (MeSH) ; Transcriptome (MeSH) ; Killer Cells, Natural: immunology (MeSH) ; Mycobacterium tuberculosis: immunology (MeSH) ; Single-Cell Analysis (MeSH) ; Monocytes: immunology (MeSH) ; Monocytes: metabolism (MeSH) ; Gene Expression Profiling (MeSH) ; Male (MeSH) ; Female (MeSH) ; T-Lymphocytes: immunology (MeSH) ; Adult (MeSH) ; Middle Aged (MeSH) ; Tuberculosis, Pulmonary: immunology (MeSH) ; Tuberculosis, Pulmonary: genetics (MeSH) ; Tuberculosis, Extrapulmonary (MeSH)

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Contributing Institute(s):

1. Clinical Single Cell Omics (CSCO) / Systems Medicine (AG Schultze)
2. Immunogenomics and Neurodegeneration (AG Beyer)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)
2. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2025

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