Frontiers in Immunology (Mar 2022)

In-Depth Immunophenotyping With Mass Cytometry During TB Treatment Reveals New T-Cell Subsets Associated With Culture Conversion

  • Carole Chedid,
  • Carole Chedid,
  • Carole Chedid,
  • Thibault Andrieu,
  • Eka Kokhreidze,
  • Nestani Tukvadze,
  • Samanta Biswas,
  • Md. Fahim Ather,
  • Mohammad Khaja Mafij Uddin,
  • Sayera Banu,
  • Flavio De Maio,
  • Giovanni Delogu,
  • Hubert Endtz,
  • Delia Goletti,
  • Marc Vocanson,
  • Oana Dumitrescu,
  • Oana Dumitrescu,
  • Oana Dumitrescu,
  • Jonathan Hoffmann,
  • Jonathan Hoffmann,
  • Florence Ader,
  • Florence Ader

DOI
https://doi.org/10.3389/fimmu.2022.853572
Journal volume & issue
Vol. 13

Abstract

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Tuberculosis (TB) is a difficult-to-treat infection because of multidrug regimen requirements based on drug susceptibility profiles and treatment observance issues. TB cure is defined by mycobacterial sterilization, technically complex to systematically assess. We hypothesized that microbiological outcome was associated with stage-specific immune changes in peripheral whole blood during TB treatment. The T-cell phenotypes of treated TB patients were prospectively characterized in a blinded fashion using mass cytometry after Mycobacterium tuberculosis (Mtb) antigen stimulation with QuantiFERON-TB Gold Plus, and then correlated to sputum culture status. At two months of treatment, cytotoxic and terminally differentiated CD8+ T-cells were under-represented and naïve CD4+ T-cells were over-represented in positive- versus negative-sputum culture patients, regardless of Mtb drug susceptibility. At treatment completion, a T-cell immune shift towards differentiated subpopulations was associated with TB cure. Overall, we identified specific T-cell profiles associated with slow sputum converters, which brings new insights in TB prognostic biomarker research designed for clinical application.

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