Deep Immunoprofiling of Large-Scale Tuberculosis Dataset at Single Cell Resolution Reveals a CD81<sup>bright</sup> γδ T Cell Population Associated with Latency
Mojtaba Shekarkar Azgomi,
Giusto Davide Badami,
Miriam Di Caro,
Bartolo Tamburini,
Miriana Fallo,
Costanza Dieli,
Kiana Ebrahimi,
Francesco Dieli,
Marco Pio La Manna,
Nadia Caccamo
Affiliations
Mojtaba Shekarkar Azgomi
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico (A.O.U.P.) Paolo Giaccone, University of Palermo, 90127 Palermo, Italy
Giusto Davide Badami
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico (A.O.U.P.) Paolo Giaccone, University of Palermo, 90127 Palermo, Italy
Miriam Di Caro
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico (A.O.U.P.) Paolo Giaccone, University of Palermo, 90127 Palermo, Italy
Bartolo Tamburini
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico (A.O.U.P.) Paolo Giaccone, University of Palermo, 90127 Palermo, Italy
Miriana Fallo
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico (A.O.U.P.) Paolo Giaccone, University of Palermo, 90127 Palermo, Italy
Costanza Dieli
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico (A.O.U.P.) Paolo Giaccone, University of Palermo, 90127 Palermo, Italy
Kiana Ebrahimi
Faculté d’Ingénierie et Management de la Santé (ILIS), Université de Lille, 59120 Loos, France
Francesco Dieli
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico (A.O.U.P.) Paolo Giaccone, University of Palermo, 90127 Palermo, Italy
Marco Pio La Manna
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico (A.O.U.P.) Paolo Giaccone, University of Palermo, 90127 Palermo, Italy
Nadia Caccamo
Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Azienda Ospedaliera Universitaria Policlinico (A.O.U.P.) Paolo Giaccone, University of Palermo, 90127 Palermo, Italy
Tuberculosis (TB) remains one of the leading causes of death among infectious diseases, with 10.6 million new cases and 1.3 million deaths reported in 2022, according to the most recent WHO report. Early studies have shown an expansion of γδ T cells following TB infection in both experimental models and humans, indicating their abundance among lung lymphocytes and suggesting a role in protective immune responses against Mycobacterium tuberculosis (M. tuberculosis) infection. In this study, we hypothesized that distinct subsets of γδ T cells are associated with either protection against or disease progression in TB. To explore this, we applied large-scale scRNA-seq and bulk RNA-seq data integration to define the phenotypic and molecular characteristics of peripheral blood γδ T cells. Our analysis identified five unique γδ T subclusters, each with distinct functional profiles. Notably, we identified a unique cluster significantly enriched in the TCR signaling pathway, with high CD81 expression as a conserved marker. This distinct molecular signature suggests a specialized role for this cluster in immune signaling and regulation of immune response against M. tuberculosis. Flow cytometry confirmed our in silico results, showing that the mean fluorescence intensity (MFI) values of CD81 expression on γδ T cells were significantly increased in individuals with latent TB infection (TBI) compared to those with active TB (ATB). This finding underscores the importance of CD81 and its associated signaling mechanisms in modulating the activity and function of γδ T cells under TBI conditions, providing insights into potential therapeutic targets for TB management.
