Abstract
Deficiencies in current tuberculosis (TB) immunodiagnostics pipeline demand new approaches to control TB. Because the balance in key pro- and anti-inflammatory cytokines production could determine Mycobacterium Tuberculosis (MTb) infection outcome, this study aimed to determine the patterns of MTb-specific antigen-stimulated Interferon-gamma (IFN-y) and Interleukin-10 (IL-10) production in different clinical forms of MTb infection and to evaluate their concomitant changes during anti-TB treatment (ATT). Overall, 84 BCG-vaccinated HIV-negative adults, consisting of 25 Healthy Community Controls (HCC), 27 Latent Tuberculosis Infection (LTBI) cases, and a cohort of 32 Acute Pulmonary Tuberculosis (APTB) patients were investigated for IFN-y and IL-10 responses at enrollment (base-line) and during ATT at 2-month (ATT1) and 6-month (ATT2). At enrollment, groups didn’t differ significantly in age, gender, or CD4+ T counts but differed in the other socio-demographics, and hematological parameters, p<0.05. Base-line Sandwich ELISA – measured IFN-y responses were significantly higher in HCC (223.50±58.11pg/ml) compared with LTBI (128.82±41.81pg/ml) and APTB (47.82±22.05pg/ml), p<0.0001 in each case. During treatment, IFN-y levels increased significantly at ATT1 (125.37±16.09pg/ml) and ATT2 (203.35±23.24pg/ml), p<0.0001. Conversely, base-line IL-10 responses increased significantly in APTB (17.53±6.30pg/ml), compared with LTBI (10.71±2.39pg/ml) and HCC (7.49±2.02pg/ml), P<0.0001, but declined significantly at ATT1 (10.54±2.25pg/ml) and ATT2 (5.25±1.45pg/ml), P=<0.0001. Cytokines response combination ratio showed: ‘High’ HCC, ‘Intermediate’ LTBI, or ‘Low’ APTB ratio that increased during successful ATT; the two identified MDR-TB patients recorded fluctuating but constantly low ratio during ATT. These results demonstrate the immunocompetence of MTb-exposed adults, and that IFN-y and IL-10 cytokines cross-regulate, and strongly suggest a shift toward IFN-y-mediated pro-inflammatory host immune phenotype during effective control of MTb infection. The IFN-y/IL-10 response ratio is a novel potential immunological biomarker to assess if MTb infection is going to resolve, result in latency, progress to TB; or become drug-resistant.
Highlights
Tuberculosis (TB) caused by mycobacterium tuberculosis (MTb) bacillus is the oldest documented infectious disease
Four participants were excluded from the final results: two 18 year-old male recruits who did not return for the TST reading, two active pulmonary tuberculosis (APTB) patients who had indeterminate INF-y and IL-10 test results respectively in our cytokine enzyme- linked immunosorbent assay (ELISA)
The enrolled participants consisted of 25 healthy community controls (HCC), 27 latent tuberculosis infection (LTBI) cases and 32 newly diagnosed active pulmonary tuberculosis (ATB) patients
Summary
Tuberculosis (TB) caused by mycobacterium tuberculosis (MTb) bacillus is the oldest documented infectious disease. It has been established that co-ordination/co-operation between the various cellular elements, especially the macrophages and CD4+T lymphocytes, which is dependent on the interplay of cytokines secreted by these cells, are critical for the control of MTb infection [4, 5, 6]. Those with cellular immune defects involving cytokine response dysregulation could be especially at risk for developing active TB. Accurate diagnosis of the clinical form of MTb infection is a cornerstone of TB control
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