Dataset Information

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

ABSTRACT:

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.

SUBMITTER: van Rensburg IC

PROVIDER: S-EPMC5322165 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

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

van Rensburg Ilana C IC Kleynhans Léanie L Keyser Alana A Walzl Gerhard G Loxton Andre G AG

Immunity, inflammation and disease 20161227 1

<h4>Introduction</h4>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 induc ...[more]

PMID: 28250925

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Project description:Background Identification of patients at risk of tuberculosis relapse following treatment would revolutionize clinical trials of new drugs and regimens and facilitate clinical management. The study aim was to determine whether tuberculosis patients who subsequently suffer relapse have different immune responses to mycobacteria in vitro compared to patients who remain cured for two years post-treatment. Methods First episode pulmonary tuberculosis patients were recruited into a surrogate marker study in Cape Town, South Africa. Peripheral blood samples were collected at diagnosis and after two and four weeks of tuberculosis treatment. Diluted blood was cultured with live Mycobacterium tuberculosis for six days and cellular RNA was frozen. Gene expression in samples from ten patients who subsequently relapsed, confirmed by stain genotyping, was compared to those who remained cured using Affymetrix microarrays. Results At diagnosis, the expression of 668 genes was significantly different in samples from patients who subsequently relapsed compared to successfully cured patients, and these differences persisted for at least four weeks. Gene Ontology and biological pathways analyses revealed the most significant difference was up-regulation of genes involved in cytotoxic cell-mediated killing, such as perforin, granulysin and fas ligand. Results were confirmed by qRT-PCR in a wider patient cohort. Conclusions These data show that patients who will subsequently relapse exhibit altered immune responses at diagnosis, including excessively robust cytolytic responses to M. tuberculosis in vitro, compared to patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited for patient stratification in drugs trials, or for host-directed therapy development. Venous blood samples were diluted in culture medium and stimulated with live M. tuberculosis for 6 days. Samples from 10 TB patients who subsequently relapsed and 10 patients whore remained disease-free for 2 years. Samples collected at TB diagnosis and after 2 weeks or 4 weeks of treatment of first TB episode.

Dataset Information

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

Introduction

Methods

Results

Conclusion

Publications

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

Similar Datasets

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