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<p>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.</p>

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Deep immune profiling delineates hallmarks of disease heterogeneity in extrapulmonary tuberculosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月10日

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  • Sebastian J. Theobald,
  • Kilian Dahm,
  • Dinah Lange,
  • Jannis B. Spintge,
  • Sandra Winter,
  • Angela Klingmüller,
  • Lisa Holsten,
  • Alexander Simonis,
  • Elena De Domenico,
  • Henning Walczak,
  • Martina van Uelft,
  • Joachim L. Schultze,
  • Marc D. Beyer,
  • Thomas Ulas,
  • Isabelle Suárez,
  • Jan Rybniker

摘要

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.