RESUMEN
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.
Asunto(s)
Trampas Extracelulares/metabolismo , Mycobacterium tuberculosis/metabolismo , Neutrófilos/metabolismo , Tuberculosis Pulmonar/sangre , Adulto , Femenino , Humanos , Masculino , Activación Neutrófila/fisiología , Tuberculosis Pulmonar/diagnóstico , Adulto JovenRESUMEN
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.
Asunto(s)
Inmunidad Innata/inmunología , Tuberculosis Pulmonar/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bangladesh/epidemiología , Femenino , Citometría de Flujo , Humanos , Interleucina-8/inmunología , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/inmunología , Receptores Toll-Like/inmunología , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/epidemiología , Adulto JovenRESUMEN
OBJECTIVE To evaluate a computer-assisted point-prevalence survey (CAPPS) for hospital-acquired infections (HAIs). DESIGN Validation cohort. SETTING A 754-bed teaching hospital in the Netherlands. METHODS For the internal validation of a CAPPS for HAIs, 2,526 patients were included. All patient records were retrospectively reviewed in depth by 2 infection control practitioners (ICPs) to determine which patients had suffered an HAI. Preventie van Ziekenhuisinfecties door Surveillance (PREZIES) criteria were used. Following this internal validation, 13 consecutive CAPPS were performed in a prospective study from January to March 2013 to determine weekly, monthly, and quarterly HAI point prevalence. Finally, a CAPPS was externally validated by PREZIES (Rijksinstituut voor Volksgezondheid en Milieu [RIVM], Bilthoven, Netherlands). In all evaluations, discrepancies were resolved by consensus. RESULTS In our series of CAPPS, 83% of the patients were automatically excluded from detailed review by the ICP. The sensitivity of the method was 91%. The time spent per hospital-wide CAPPS was ~3 hours. External validation showed a negative predictive value of 99.1% for CAPPS. CONCLUSIONS CAPPS proved to be a sensitive, accurate, and efficient method to determine serial weekly point-prevalence HAI rates in our hospital. Infect Control Hosp Epidemiol 2016;1-6.
Asunto(s)
Infección Hospitalaria/epidemiología , Toma de Decisiones Asistida por Computador , Técnicas de Apoyo para la Decisión , Vigilancia de Guardia , Algoritmos , Estudios de Cohortes , Infección Hospitalaria/diagnóstico , Hospitales Generales , Humanos , Profesionales para Control de Infecciones , Entrevistas como Asunto , Registros Médicos , Países Bajos/epidemiología , PrevalenciaRESUMEN
Tuberculosis (TB) is an important cause of morbidity and mortality worldwide. Granzymes (gzms) are proteases mainly found in cytotoxic lymphocytes, but also extracellularly. While the role of gzms in target cell death has been widely characterized, considerable evidence points towards broader roles related to infectious and inflammatory responses. To investigate the expression of the gzms in TB, intracellular gzms A, B and K were measured by flow cytometry in lymphocyte populations from peripheral blood mononuclear cells from 18 TB patients and 12 healthy donors from Bangladesh, and extracellular levels of gzmA and B were measured in serum from 58 TB patients and 31 healthy controls. TB patients showed increased expression of gzmA in CD8(+) T, CD4(+) T and CD56(+) T, but not NK, cells, and of gzmB in CD8(+) T cells, when compared to controls. GzmK expression was not altered in TB patients in any lymphocyte subset. The extracellular levels of gzmA and, to a lesser extent, of gzmB, were increased in TB patients, but did not correlate with intracellular gzm expression in lymphocyte subsets. Our results reveal enhanced intra- and extracellular expression of gzmA and B in patients with pulmonary TB, suggesting that gzms are part of the host response to tuberculosis.
Asunto(s)
Granzimas/sangre , Linfocitos T/enzimología , Tuberculosis/sangre , Tuberculosis/enzimología , Adulto , Bangladesh , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Interacciones Huésped-Patógeno , Humanos , Masculino , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/patogenicidad , Linfocitos T/inmunología , Linfocitos T/microbiología , Tuberculosis/diagnóstico , Tuberculosis/inmunología , Tuberculosis/microbiología , Regulación hacia Arriba , Adulto JovenRESUMEN
OBJECTIVES: Human tuberculosis (TB) remains an important cause of death globally. Bangladesh is one of the most affected countries. We aimed to investigate the impact of pulmonary TB on pro- and anticoagulant mechanisms. METHODS: This prospective study was conducted in Chittagong, Bangladesh. We performed an in-depth analysis of coagulation activation and inhibition in plasma obtained from 64 patients with primary lung TB and 11 patients with recurrent lung TB and compared these with 37 healthy controls. Additionally, in nine patients coagulation activation was studied in bronchoalveolar lavage fluid (BALF) harvested from the site of infection and compared with BALF from a contralateral unaffected lung subsegment. RESULTS: Relative to uninfected controls, primary and recurrent TB were associated with a systemic net procoagulant state, as indicated by enhanced activation of coagulation (elevated plasma levels of thrombin-antithrombin complexes, D-dimer and fibrinogen) together with impaired anticoagulant mechanisms (reduced plasma levels of antithrombin, protein C activity, free protein S, and protein C inhibitor). Activation of coagulation did not correlate with plasma concentrations of established TB biomarkers. Coagulation activation could not be detected at the primary site of infection in a subset of TB patients. CONCLUSIONS: Pulmonary TB is associated with a systemic hypercoagulable state.