Deep immune profiling delineates hallmarks of disease heterogeneity in extrapulmonary tuberculosis
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.
Authors
- Thomas Ulas (ORCID: https://orcid.org/0000-0002-9785-4197)
- Lisa Holsten (ORCID: https://orcid.org/0000-0001-6238-1273)
- Marc Beyer (ORCID: https://orcid.org/0000-0001-9704-148X)
- Jan Rybniker (ORCID: https://orcid.org/0000-0001-8351-2690)
- Elena De Domenico (ORCID: https://orcid.org/0000-0003-0336-8284)
- Alexander Simonis (ORCID: https://orcid.org/0000-0003-2945-9897)
- K. Dahm (ORCID: https://orcid.org/0000-0002-6819-2622)
- Angela Klingmüller
- Sebastian J. Theobald
- Martina van Uelft
- Sandra Winter
- Joachim L. Schultze (ORCID: https://orcid.org/0000-0003-2812-9853)
- Isabelle Suárez
- Henning Walczak (ORCID: https://orcid.org/0000-0002-6312-4591)
- Jannis Bastian Spintge (ORCID: https://orcid.org/0009-0006-7826-9781)
- Dinah Lange (ORCID: https://orcid.org/0000-0002-2933-2143)
Institutions
- University of Bonn (DE)
- University of Cologne (DE)
- German Center for Neurodegenerative Diseases (DE)
- German Center for Infection Research (DE)
- Universitätsklinikum Würzburg (DE)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- CRUK Lung Cancer Centre of Excellence (GB)
- University Hospital Cologne (DE)
- University College London (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-10
- DOI
- https://doi.org/10.1038/s41467-025-65561-x
- Citations
- 2
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 2.79