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.

Highlights

  • T-cell driven cell-mediated immunity, has been the focus of studies investigating host immunity against M.tb infection [1]-[3] and TB disease

  • We show that FASLG, IL5RA, cluster of differentiation 38 (CD38) and IL4 expression was lower in B-cells from TB cases compared to healthy controls

  • When comparing the expression of the genes between healthy controls and TB cases, we found that there was a significant decrease in the expression of IL4, FASLG, IL5RA and CD38 (p < 0.05) (Table 2)

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Summary

Introduction

T-cell driven cell-mediated immunity, has been the focus of studies investigating host immunity against M.tb infection [1]-[3] and TB disease. An increasing number of studies are indicating that the role of B-cells in the protective immunity against M.tb infection has been underestimated. B-cells are the key players during humoral immunity and produce antibodies in response to invading pathogens. Studies found that humoral immunity may enhance protection against M.tb infection [4]-[6]. B-cells have additional functions that may be essential for host protection during infection and disease. Activated B-cells change T-cell behaviour during autoimmune disease and other pathogenic infections by means of cytokine production and antigen-presentation

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