Successful TB treatment induces B-cells expressing FASL and IL5RA mRNA.
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.
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.
Ilana C
IC
van Rensburg
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.
Chandre
C
Wagman
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.
Kim
K
Stanley
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.
Caroline
C
Beltran
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.
Katharina
K
Ronacher
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.
Gerhard
G
Walzl
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.
Andre G
AG
Loxton
D000995:Antitubercular Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D054316:Biomarkers, Pharmacological; D016022:Case-Control Studies; D016903:Drug Monitoring / Q000379:methods; D053222:Fas Ligand Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053666:Interleukin-5 Receptor alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008297:Male; D010865:Pilot Projects; D011379:Prognosis; D012333:RNA, Messenger / Q000187:drug effects; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology
D000995:Antitubercular Agents; D015415:Biomarkers; D054316:Biomarkers, Pharmacological; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C485918:IL5RA protein, human; D053666:Interleukin-5 Receptor alpha Subunit; D012333:RNA, Messenger
B-cells; FasL; IL5Ra; Immune response; Immunity; Immunology and Microbiology Section; TB treatment; regulatory cells
J Immunol. 2007 Sep 15;179(6):3821-30
17785819
Nature. 2010 Aug 19;466(7309):973-7
20725040
IUBMB Life. 2011 Oct;63(10):840-6
21901817
Eur J Immunol. 2001 Dec;31(12):3460-8
11745365
Inflamm Res. 2009 Jul;58(7):345-57
19262989
J Immunol Res. 2015;2015:217287
26339657
Infect Immun. 2005 Oct;73(10):6711-20
16177348
Eur J Immunol. 2010 Aug;40(8):2211-20
20540114
Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):E2199-208
23716674
Nature. 2014 Mar 20;507(7492):366-70
24572363
J Immunol. 2007 Jun 1;178(11):7222-34
17513771
J Exp Med. 1999 Jan 4;189(1):1-12
9874559
Sci Rep. 2012;2:216
22355730
J Immunol. 2004 Jan 15;172(2):954-63
14707068
N Engl J Med. 2014 May 1;370(18):1712-23
24785206
Eur J Immunol. 2001 Apr;31(4):1261-7
11298353
Biomark Med. 2015;9(5):483-95
25985177
Eur J Immunol. 2007 Feb;37(2):358-67
17274001
J Infect Dis. 2013 Jan 1;207(1):18-29
22872737
J Leukoc Biol. 2000 Apr;67(4):457-63
10770276
Eur J Immunol. 2009 Mar;39(3):676-86
19283721
PLoS One. 2013 Aug 05;8(8):e70131
23940537
Mol Immunol. 2009 Apr;46(7):1278-88
19157556