Oncotarget

Research Papers: Immunology:

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

Ilana C. van Rensburg, Chandre Wagman, Kim Stanley, Caroline Beltran, Katharina Ronacher, Gerhard Walzl and Andre G. Loxton _

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Oncotarget. 2017; 8:2037-2043. https://doi.org/10.18632/oncotarget.12184

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Abstract

Ilana C. van Rensburg1, Chandre Wagman1, Kim Stanley1, Caroline Beltran1, Katharina Ronacher1, Gerhard Walzl1 and Andre G. Loxton1

1 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

Correspondence to:

Andre G. Loxton, email:

Keywords: FasL, IL5Ra, B-cells, regulatory cells, TB treatment, Immunology and Microbiology Section, Immune response, Immunity

Received: March 31, 2016 Accepted: September 13, 2016 Published: September 22, 2016

Abstract

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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