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

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.853572

DOI=10.3389/fimmu.2022.853572

ISSN=1664-3224

ABSTRACT=<p>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 <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) antigen stimulation with QuantiFERON-TB Gold Plus, and then correlated to sputum culture status. At two months of treatment, cytotoxic and terminally differentiated CD8<sup>+</sup> T-cells were under-represented and naïve CD4<sup>+</sup> T-cells were over-represented in positive- <italic>versus</italic> negative-sputum culture patients, regardless of <italic>Mtb</italic> 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.</p>