B‐cells with a FasL expressing regulatory phenotype are induced following successful anti‐tuberculosis treatment

• Published in: Immunity, Inflammation and Disease Inflammation and Disease, 2017-03, Vol.5 (1), p.57-67
• Main Authors: van Rensburg, Ilana C., Kleynhans, Léanie, Keyser, Alana, Walzl, Gerhard, Loxton, Andre G.
• Format: Article
• Language: English
• Subjects: Antitubercular Agents - pharmacology; Antitubercular Agents - therapeutic use; Apoptosis; Asthma; Autoimmune diseases; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Bronchoalveolar Lavage Fluid - immunology; broncho‐alveolar lavage fluid; Cytokines; Cytokines - blood; Cytokines - immunology; Fas Ligand Protein - genetics; FasL; Flow cytometry; Gene expression; Gene Expression Regulation - drug effects; Genotype & phenotype; Humans; Hypotheses; immune exhaustion; Infections; Inflammation; Interleukin-5 Receptor alpha Subunit - genetics; Laboratories; Original Research; Phenotype; Studies; Tuberculosis; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - genetics; Tuberculosis, Pulmonary - immunology; Tumor necrosis factor-TNF
• ISSN: 2050-4527; 2050-4527
• DOI: 10.1002/iid3.140

Introduction Studies show that B‐cells, in addition to producing antibodies and antigen‐presentation, are able to produce cytokines as well. These include regulatory cytokines such as IL‐10 by regulatory B‐cells. Furthermore, a rare regulatory subset of B‐cells have the potential to express FasL, which is a death‐inducing ligand. This subset of B‐cells have a positive role during autoimmune disease, but has not yet been studied during tuberculosis. These FasL‐expressing B‐cells are induced by bacterial LPS and CpG, thus we hypothesized that this phenotype might be induced during tuberculosis as well. Methods B‐cells from participants with TB (at diagnosis and during treatment) and controls were collected, and analyzed by means of real‐time PCR and flow cytometry. In addition to this, BAL was collected from TB participants as well and analyzed by means of MAGPix (multi‐cytokine) technology. Results Gene expression analysis show that FASL transcript levels increase by the end of treatment. Similarly, phenotypic analysis show that there is a higher frequency of FasL‐expressing B‐cells by the end of treatment. Conclusion Collectively, these results indicate that these FasL‐expressing B‐cells are being induced during anti‐TB treatment, and thus may play a positive role. Further studies are required to elucidate this. Successful Tuberculosis treatment induces B‐lymphocytes expressing the FasL receptor that may be important for protection. Regulatory (killer) B cells may have an important role as part of restoration of the immune system.