ABSTRACT
Tuberculosis is a devastating infectious disease causing many deaths worldwide. Recent investigations have implicated neutrophil extracellular traps (NETs) in the host response to tuberculosis. The aim of the current study was to obtain evidence for NETs release in the circulation during human tuberculosis. For this we measured the plasma concentrations of nucleosomes in conjunction with neutrophil elastase, in 64 patients with active pulmonary tuberculosis and 32 healthy controls. Patients with active tuberculosis had elevated plasma levels of nucleosomes and elastase when compared with local healthy blood donors. Furthermore nucleosome and elastase levels showed a positive correlation. These findings provide the first evidence for the release of NETs in the circulation of patients with active pulmonary tuberculosis.
Subject(s)
Extracellular Traps/metabolism , Mycobacterium tuberculosis/metabolism , Neutrophils/metabolism , Tuberculosis, Pulmonary/blood , Adult , Female , Humans , Male , Neutrophil Activation/physiology , Tuberculosis, Pulmonary/diagnosis , Young AdultABSTRACT
BACKGROUND: Tuberculosis (TB) is an important cause of morbidity and mortality worldwide. Toll-like-receptors (TLRs) are important for the recognition of the causative agent Mycobacterium tuberculosis. Negative regulation of TLRs is necessary to control deleterious inflammatory damage, but could provide a means of immune evasion by M. tuberculosis as well. METHODS: To obtain insight in the extent of expression of inhibitory regulators of immunity in patients with active TB, peripheral-blood-mononuclear-cells (PBMCs) and plasma were obtained from 54 TB patients and 29 healthy blood donors from Chittagong, Bangladesh. Bilateral alveolar macrophages were obtained from an infected versus a contralateral normal lung segment of 9 patients. Statistical analyses were performed using Mann-Whitney U and Wilcoxon matched pairs testing. Correlations were calculated using the Spearman rho test. RESULTS: PBMCs harvested from TB patients demonstrated increased mRNA expression of IL-1-receptor-associated-kinase-M, suppressor-of-cytokine-signalling-3 and Toll-interacting-protein. Flow cytometry revealed enhanced expression of IL-1-receptor-like-1 (ST2) on lymphocytes. Plasma soluble ST2 was elevated in patients with TB and correlated with established TB biomarkers, most strongly with soluble interleukin-2 receptor subunit α and interleukin-8. Alveolar macrophage mRNA expression of negative TLR regulators did not differ between the infected and contralateral lung side. CONCLUSION: These results show enhanced expression of distinct negative regulators of innate immunity in PBMCs of patients with TB and identify plasma soluble ST2 as a potential novel biomarker for TB disease activity.
Subject(s)
Immunity, Innate/immunology , Tuberculosis, Pulmonary/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Bangladesh/epidemiology , Female , Flow Cytometry , Humans , Interleukin-8/immunology , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Mycobacterium tuberculosis/immunology , Toll-Like Receptors/immunology , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/epidemiology , Young AdultABSTRACT
BACKGROUND: There are limited data on TB among prison inmates in Bangladesh. The aim of the study was to determine the prevalence of pulmonary tuberculosis (TB), its drug resistance and risk factors in Dhaka Central Jail, the largest prison in Bangladesh. METHODS: Cross sectional survey with, active screening of a total number of 11,001 inmates over a period of 2 years. Sputum samples from TB suspects were taken for acid- fast bacilli (AFB) microscopy, culture and drug susceptibility testing. RESULTS: Among 1,781 TB suspects 245 (13.8%) were positive for AFB on microscopy and/or culture. The prevalence rate of sputum- positive pulmonary TB was 2,227/100,000. Fifty three cases (21.6% of 245 cases) were AFB- negative on microscopy but were found positive on culture. Resistance to isoniazid, rifampicin, streptomycin and ethambutol was 11.4%, 0.8%, 22.4% and 6.5% respectively. No multidrug resistance was observed. The main risk factors of TB in prison were exposure to TB patients (adjusted odds ratio 3.16, 95% CI 2.36-4.21), previous imprisonment (1.86, 1.38-2.50), longer duration of stay in prison (17.5 months for TB cases; 1.004, 1.001-1.006) and low body mass index which is less than 18.5 kg/m(2) (5.37, 4.02-7.16). CONCLUSIONS: The study results revealed a very high prevalence of TB in the prison population in Dhaka Central Jail. Entry examinations and active symptom screening among inmates are important to control TB transmission inside the prison. Identifying undiagnosed smear-negative TB cases remains a challenge to combat this deadly disease in this difficult setting.
