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Unravelling the transcriptome of the human tuberculosis lesion and its clinical implications

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  • Kaori L. Fonseca

    (Fundació Institut Germans Trias i Pujol (IGTP)
    Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES))

  • Juan José Lozano

    (Centro de Investigación Biomédica en Red de Enfermedades Hepática y Digestivas (CIBERehd)
    Hospital Clínic de Barcelona)

  • Albert Despuig

    (Fundació Institut Germans Trias i Pujol (IGTP)
    Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES))

  • Dominic Habgood-Coote

    (Imperial College London)

  • Julia Sidorova

    (Centro de Investigación Biomédica en Red de Enfermedades Hepática y Digestivas (CIBERehd)
    Hospital Clínic de Barcelona)

  • Diego Aznar

    (Fundació Institut Germans Trias i Pujol (IGTP)
    Universitat Autònoma de Barcelona (UAB))

  • Lilibeth Arias

    (Fundació Institut Germans Trias i Pujol (IGTP)
    Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES))

  • Álvaro Del Río-Álvarez

    (Germans Trias i Pujol Research Institute (IGTP)
    Germans Trias i Pujol Research Institute (IGTP)
    Liver and Digestive Diseases Networking Biomedical Research Centre (CIBER))

  • Juan Carrillo-Reixach

    (Germans Trias i Pujol Research Institute (IGTP)
    Germans Trias i Pujol Research Institute (IGTP)
    Liver and Digestive Diseases Networking Biomedical Research Centre (CIBER))

  • Aaron Goff

    (University of Sussex)

  • Leticia Muraro Wildner

    (University of Sussex)

  • Shota Gogishvili

    (National Center for Tuberculosis and Lung Diseases (NCTLD))

  • Keti Nikolaishvili

    (National Center for Tuberculosis and Lung Diseases (NCTLD))

  • Natalia Shubladze

    (National Center for Tuberculosis and Lung Diseases (NCTLD))

  • Zaza Avaliani

    (National Center for Tuberculosis and Lung Diseases (NCTLD)
    European University)

  • Gustavo Tapia

    (Hospital Germans Trias i Pujol
    Universitat Autònoma de Barcelona)

  • Paula Rodríguez-Martínez

    (Hospital Germans Trias i Pujol
    Universitat Autònoma de Barcelona)

  • Pere-Joan Cardona

    (Fundació Institut Germans Trias i Pujol (IGTP)
    Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES)
    Universitat Autònoma de Barcelona (UAB)
    Hospital Universitari Germans Trias i Pujol)

  • Federico Martinón-Torres

    (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES)
    Instituto de Investigación Sanitaria de Santiago (IDIS)
    Universidad de Santiago de Compostela (USC)
    Hospital Clínico Universitario de Santiago de Compostela (SERGAS))

  • Antonio Salas

    (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES)
    Hospital Clínico Universitario de Santiago de Compostela (SERGAS)
    Universidade de Santiago de Compostela
    Instituto de Investigación Sanitaria (IDIS))

  • Alberto Gómez-Carballa

    (Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES)
    Hospital Clínico Universitario de Santiago de Compostela (SERGAS)
    Universidade de Santiago de Compostela
    Instituto de Investigación Sanitaria (IDIS))

  • Carolina Armengol

    (Germans Trias i Pujol Research Institute (IGTP)
    Germans Trias i Pujol Research Institute (IGTP)
    Liver and Digestive Diseases Networking Biomedical Research Centre (CIBER))

  • Simon J. Waddell

    (University of Sussex)

  • Myrsini Kaforou

    (Imperial College London
    Imperial College London)

  • Anne O’Garra

    (The Francis Crick Institute
    Imperial College)

  • Sergo Vashakidze

    (National Center for Tuberculosis and Lung Diseases (NCTLD)
    The University of Georgia)

  • Cristina Vilaplana

    (Fundació Institut Germans Trias i Pujol (IGTP)
    Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES)
    Universitat Autònoma de Barcelona (UAB)
    Hospital Universitari Germans Trias i Pujol)

Abstract

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.

Suggested Citation

  • Kaori L. Fonseca & Juan José Lozano & Albert Despuig & Dominic Habgood-Coote & Julia Sidorova & Diego Aznar & Lilibeth Arias & Álvaro Del Río-Álvarez & Juan Carrillo-Reixach & Aaron Goff & Leticia Mur, 2025. "Unravelling the transcriptome of the human tuberculosis lesion and its clinical implications," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60255-w
    DOI: 10.1038/s41467-025-60255-w
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