Publications by authors named "Ilana C van Rensburg"

6 Publications

  • Page 1 of 1

FasL regulatory B-cells during Mycobacterium tuberculosis infection and TB disease.

J Mol Biol 2021 Apr 21:166984. Epub 2021 Apr 21.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town 8000, South Africa. Electronic address:

Tuberculosis (TB) disease remains a major health crisis. Infection with Mycobacterium tuberculosis (M.tb) cause a range of diseases ranging from latent infection to active TB disease. This active state of the disease is characterised by the formation of granulomas (a physical barrier in the lung), a structure thought to protect the host by controlling the infection through preventing the growth of the bacilli. Subsequently, the surviving bacteria become inactive and in most cases, TB reactivation is prevented by the immune response of the host. B-cells perform numerous immunological functions beyond antibody production to positively regulate the response to pathogenic assault. A subgroup of B-cells with regulatory functions express death-inducing ligands, such as Fas ligand (FasL). Expression and interaction of the Fas receptor-ligand promotes the induction of apoptosis and the induction of T-cell tolerance. Here, we focus on the significance of B-cells by addressing their FasL phenotype and regulatory functions during TB, with reference to disease in humans, non-human primates and mice.
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http://dx.doi.org/10.1016/j.jmb.2021.166984DOI Listing
April 2021

Immunoglobulin profile and B-cell frequencies are altered with changes in the cellular microenvironment independent of the stimulation conditions.

Immun Inflamm Dis 2020 09 8;8(3):458-467. Epub 2020 Jul 8.

Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.

Introduction: B-cells are essential in the defense against Mycobacterium tuberculosis. Studies on isolated cells may not accurately reflect the responses that occur in vivo due to the presence of other cells. This study elucidated the influence of microenvironment complexity on B-cell polarization and function in the context of tuberculosis disease.

Methods: B-cell function was tested in whole blood, peripheral blood mononuclear cells (PBMCs), and as isolated cells. The different fractions were stimulated and the B-cell phenotype and immunoglobulin profiles analyzed.

Results: The immunoglobulin profile and developmental B-cell frequencies varied for each of the investigated sample types, while in an isolated cellular environment, secretion of immunoglobulin isotypes immunoglobulin A (IgA), IgG2, and IgG3 was hampered. The differences in the immunoglobulin profile highlight the importance of cell-cell communication for B-cell activation. Furthermore, a decrease in marginal zone B-cell frequencies and an increase in T1 B-cells was observed following cell isolation, indicating impaired B-cell development in response to in vitro antigenic stimulation in isolation.

Conclusion: Our results suggest that humoral B-cell function and development was impaired likely due to a lack of costimulatory signals from other cell types. Thus, B-cell function should ideally be studied in a PBMC or whole blood fraction.
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http://dx.doi.org/10.1002/iid3.328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416019PMC
September 2020

Killer (FASL regulatory) B cells are present during latent TB and are induced by BCG stimulation in participants with and without latent tuberculosis.

Tuberculosis (Edinb) 2018 01 24;108:114-117. Epub 2017 Nov 24.

SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 241, Cape Town, 8000, South Africa. Electronic address:

Regulatory B cells (Bregs) have been shown to be present during several disease states. The phenotype of the cells is not completely defined and the function of these cells differ between disease. The presence of FASL expressing (killer) B cells during latent and successfully treated TB disease have been shown but whether these cells are similar to regulatory B cells remain unclear. We assessed the receptor expression of FASL/IL5 (killer B cells), CD24/CD38 (regulatory B cells) on whole peripheral blood of participants with untreated active TB and healthy controls. We then isolated B cells from a second cohort of M.tb exposed (Quantiferon (QFN) positive) and unexposed (Quantiferon negative) HIV negative participants, and evaluated the frequency of killer B cells induced following stimulation with BCG and/or CD40 and IL5. Our data reveal no difference in the expression on CD24 and CD38 between participants with active TB and the controls. There was also no difference in the frequency of regulatory B cells measured in the peripheral blood mononuclear cells (PBMC) fraction between latent TB and uninfected controls. We did however notice that regulatory B cells (CD24hiCD38hi) population express the FASL receptor. The expression of killer B cell phenotype (CD178+IL5RA+) was significantly higher in controls compared to those with active TB disease (1,06% vs 0,455%). Furthermore, we found that BCG restimulation significantly induced the FASL/IL5RA B cells but this was only evident in the QFN positive group. Our data suggest that both regulatory and killer B cells are present during latent and active TB disease but that the frequency of these populations are increased during latent disease. We also show that the FASL+IL5RA+ B killer B cells are induced in latent TB infection following BCG restimulation but whether these cells are indicative of protection remains unclear.
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http://dx.doi.org/10.1016/j.tube.2017.11.010DOI Listing
January 2018

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

Immun Inflamm Dis 2017 03 27;5(1):57-67. Epub 2016 Dec 27.

Division of Molecular Biology and Human Genetics Faculty of Medicine and Health Sciences SA MRC Centre for TB Research DST/NRF Centre of Excellence for Biomedical Tuberculosis Research Stellenbosch University Cape Town South Africa.

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.
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http://dx.doi.org/10.1002/iid3.140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322165PMC
March 2017

Successful TB treatment induces B-cells expressing FASL and IL5RA mRNA.

Oncotarget 2017 Jan;8(2):2037-2043

SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Activated B-cells increase T-cell behaviour during autoimmune disease and other infections by means of cytokine production and antigen-presentation. Functional studies in experimental autoimmune encephalomyelitis (EAE) indicate that B-cell deficiencies, and a lack of IL10 and IL35 leads to a poor prognosis. We hypothesised that B-cells play a role during tuberculosis. We evaluated B-cell mRNA expression using real-time PCR from healthy community controls, individuals with other lung diseases and newly diagnosed untreated pulmonary TB patients at three different time points (diagnosis, month 2 and 6 of treatment).We show that FASLG, IL5RA, CD38 and IL4 expression was lower in B-cells from TB cases compared to healthy controls. The changes in expression levels of CD38 may be due to a reduced activation of B-cells from TB cases at diagnosis. By month 2 of treatment, there was a significant increase in the expression of APRIL and IL5RA in TB cases. Furthermore, after 6 months of treatment, APRIL, FASLG, IL5RA and CD19 were upregulated in B-cells from TB cases. The increase in the expression of APRIL and CD19 suggests that there may be restored activation of B-cells following anti-TB treatment. The upregulation of FASLG and IL5RA indicates that B-cells expressing regulatory genes may play an important role in the protective immunity against M.tb infection. Our results show that increased activation of B-cells is present following successful TB treatment, and that the expression of FASLG and IL5RA could potentially be utilised as a signature to monitor treatment response.
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http://dx.doi.org/10.18632/oncotarget.12184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356777PMC
January 2017

Transcriptomics: the key to biomarker discovery during tuberculosis?

Biomark Med 2015 ;9(5):483-95

Tuberculosis is a global threat affecting millions of people and requires more efficient methods of diagnosis, monitoring treatment response and the development of more efficacious drug therapies and new vaccines. The use of transcriptomic approaches and gene expression techniques have contributed to the elucidation of these aspects concerning the study of tuberculosis, and more specifically, the utilization of transcriptional profiles to identify biomarkers. These markers are the key to developing tools required to improve diagnosis and treatment of tuberculosis. Several studies have led to the identification of markers able to distinguish between different infection states, as well as other pulmonary diseases. Utilizing a systems biology approach will assist in obtaining more reliable results, leading to the implementation of significant findings.
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http://dx.doi.org/10.2217/bmm.15.16DOI Listing
April 2016