Unravelling the transcriptome of the human tuberculosis lesion and its clinical implications
The tuberculosis (TB) lesion is a complex structure, contributing to the overall spectrum of TB. We characterise, using RNA sequencing, 44 fresh human pulmonary TB lesion samples from 13 TB individuals (drug-sensitive and multidrug-resistant TB) undergoing therapeutic surgery. We confirm clear separation between the TB lesion and adjacent non-lesional tissue, with the lesion samples consistently displaying increased inflammatory profile despite heterogeneity. Using weighted correlation network analysis, we identify 17 transcriptional modules associated with TB lesion and demonstrate a gradient of immune-related transcript abundance according to spatial organization of the lesion. Furthermore, we associate the modular transcriptional signature of the TB lesion with clinical surrogates of treatment efficacy and TB severity. We show that patients with worse disease present an overabundance of immune/inflammation-related modules and downregulated tissue repair and metabolism modules. Our findings provide evidence of a relationship between clinical parameters, treatment response and immune signatures at the infection site.
Authors
- Père-Joan Cardona (ORCID: https://orcid.org/0000-0001-5623-7873)
- Antonio Salas (ORCID: https://orcid.org/0000-0002-2336-702X)
- Dominic Habgood-Coote (ORCID: https://orcid.org/0000-0001-5501-0335)
- Albert Despuig (ORCID: https://orcid.org/0000-0001-9524-4355)
- Anne O’Garra (ORCID: https://orcid.org/0000-0001-9845-6134)
- Juan José Lozano (ORCID: https://orcid.org/0000-0001-7613-3908)
- Zaza Avaliani (ORCID: https://orcid.org/0000-0002-8790-3282)
- Aaron Goff
- Julia Sidorova (ORCID: https://orcid.org/0000-0002-1024-168X)
- Myrsini Kaforou (ORCID: https://orcid.org/0000-0001-9878-4007)
- Sergo A. Vashakidze (ORCID: https://orcid.org/0000-0001-5907-4870)
- Kaori L. Fonseca (ORCID: https://orcid.org/0000-0002-7048-9740)
- Letícia Muraro Wildner (ORCID: https://orcid.org/0000-0003-2553-3244)
- Natalia Shubladze (ORCID: https://orcid.org/0000-0003-0580-9629)
- Alberto Gómez‐Carballa (ORCID: https://orcid.org/0000-0003-0927-1272)
- Cristina Vilaplana (ORCID: https://orcid.org/0000-0002-2808-7270)
- Federico Martinón‐Torres (ORCID: https://orcid.org/0000-0002-9023-581X)
- Simon J. Waddell (ORCID: https://orcid.org/0000-0002-3684-9116)
- Paula Rodríguez‐Martínez
- Keti Nikolaishvili
- Juan Carrillo-Reixach (ORCID: https://orcid.org/0000-0002-8538-8264)
- Gustavo Tapia (ORCID: https://orcid.org/0000-0003-1882-0368)
- Shota Gogishvili
- Álvaro Del Río-Álvarez (ORCID: https://orcid.org/0000-0003-2338-0782)
- Carolina Armengol (ORCID: https://orcid.org/0000-0002-4690-4027)
- Lilibeth Arias (ORCID: https://orcid.org/0000-0002-2469-8832)
- Diego Aznar
Institutions
- Brighton and Sussex Medical School (GB)
- Universitat Autònoma de Barcelona (ES)
- University of Sussex (GB)
- Universidade de Santiago de Compostela (ES)
- The Francis Crick Institute (GB)
- Complejo Hospitalario Universitario de Santiago (ES)
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (ES)
- Hospital Clínic de Barcelona (ES)
- National Center for Tuberculosis and Lung Disease (GE)
- University of Georgia (GE)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
- Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (ES)
- Instituto de Investigación Sanitaria de Santiago (ES)
- Hospital Universitari Germans Trias i Pujol (ES)
- Medical Research Network (US)
- Imperial College London (GB)
- Royal College of Paediatrics and Child Health (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-30
- DOI
- https://doi.org/10.1038/s41467-025-60255-w
- Citations
- 8
- Primary Topic
- Tuberculosis Research and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 11.17
Funders
- Wellcome Trust
- Francis Crick Institute
- Cancer Research UK
- National Institute for Health and Care Research
- Imperial College London
- European Commission
- National Centre for the Replacement, Refinement and Reduction of Animals in Research
- Sociedad Española de Neumología y Cirugía Torácica
- Medical Research Council
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- Institut de Recerca contra la Leucèmia Josep Carreras