Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility.

Introduction: Tuberculosis (TB) is now the 2nd leading infectious killer after COVID-19 and the 13th leading cause of death worldwide. Moreover, TB is a lethal combination for HIV-patients. Th1 responses and particularly IFN-γ are crucial for immune protection against Mycobacterium tuberculosis infection.

[Multilevel tuberculous spondylitis].

A case of a 20-year-old man with multilevel non-contiguous tuberculous spondylitis (cervical, dorsal 6, dorsal 10 and lumbar) is presented. In the context of disseminated tuberculosis in an HIV-negative patient with serious compromise of his general condition and multiple locations of the disease, some of these with fistulas that secreted caseum. The acute paraplegia led, considering the sensory level at dorsal 6, to a first urgent decompression surgery via the posterior approach.

Effect of gene-gene and gene-environment interactions associated with antituberculosis drug-induced hepatotoxicity.

Objectives: This study evaluated the association between environmental factors and genetic variations in enzymes that metabolize antituberculosis (anti-TB) drugs [arylamine N-acetyltransferase 2, cytochrome P450 2E1 (CYP2E1), glutathione S-transferase theta 1 (GSTT1), and glutathione S-transferase mu 1] with antituberculosis drug-induced hepatotoxicity (ATDH). We also investigated the potential gene-gene and gene-environment interactions as well as their association with ATDH development in a population of hospitalized TB patients from Buenos Aires.

Patients And Methods: We investigated 364 TB patients who received anti-TB drugs.

Restimulation-induced T-cell death through NTB-A/SAP signaling pathway is impaired in tuberculosis patients with depressed immune responses.

Production of IFN-γ contributes to host defense against Mycobacterium tuberculosis (Mtb) infection. We previously demonstrated that Signaling lymphocytic activation molecule-associated protein (SAP) expression on cells from tuberculosis (TB) patients was inversely correlated with IFN-γ production. Here we first investigated the role of NK, T- and B-cell antigen (NTB-A)/SAP pathway in the regulation of Th1 response against Mtb.

tagSNP rs1495741 as a useful molecular marker to predict antituberculosis drug-induced hepatotoxicity.

Introduction: It has been widely reported that the slow acetylator phenotype of N-acetyltransferase 2 (NAT2) is associated with the development of antituberculosis drug-induced hepatotoxicity (ATDH). The aim of this report was to evaluate the level of agreement and accuracy of two recently recommended markers, the two-single nucleotide polymorphisms (SNP) (C282T and T341C) and tagSNP of NAT2 (rs1495741) genotypes, to predict the seven-SNP-inferred NAT2 phenotype in Bolivian and Argentinian tuberculosis (TB)-patient populations. In addition, we analyzed the association of these markers with ATDH.

A Mycobacterium tuberculosis Dormancy Antigen Differentiates Latently Infected Bacillus Calmette-Guérin-vaccinated Individuals.

IFN-γ release assays (IGRAs) are better indicators of Mycobacterium tuberculosis infection than the tuberculin skin test (TST) in Bacillus Calmette-Guérin (BCG)-vaccinated populations. However, IGRAs do not discriminate active and latent infections (LTBI) and no gold standard for LTBI diagnosis is available. Thus, since improved tests to diagnose M.

IFNG-mediated immune responses enhance autophagy against Mycobacterium tuberculosis antigens in patients with active tuberculosis.

Protective immunity against Mycobacterium tuberculosis (Mtb) requires IFNG. Besides, IFNG-mediated induction of autophagy suppresses survival of virulent Mtb in macrophage cell lines. We investigated the contribution of autophagy to the defense against Mtb antigen (Mtb-Ag) in cells from tuberculosis patients and healthy donors (HD).

Human pleural B-cells regulate IFN-γ production by local T-cells and NK cells in a Mycobacterium tuberculosis-induced delayed hypersensitivity reaction.

DTH (delayed type hypersensitivity) reactions are secondary cellular immune responses that appear 24-72 h after antigen exposure. Tuberculous pleurisy is a common manifestation of extrapulmonary TB (tuberculosis) and is considered a human model of Th1-mediated DTH. In order to identify functional cross-talk among cellular populations sited in this inflammatory microenvironment, we analysed phenotypic and functional features of human B-cells isolated from the PF (pleural fluid) of TB patients.

The impact of IFN-γ receptor on SLPI expression in active tuberculosis: association with disease severity.

Interferon (IFN)-γ displays a critical role in tuberculosis (TB), modulating the innate and adaptive immune responses. Previously, we reported that secretory leukocyte protease inhibitor (SLPI) is a pattern recognition receptor with anti-mycobacterial activity against Mycobacterium tuberculosis (Mtb). Herein, we determined whether IFN-γ modulated the levels of SLPI in TB patients.

Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK.

Tuberculosis (TB) is one of the world's most pernicious diseases mainly due to immune evasion strategies displayed by its causative agent Mycobacterium tuberculosis (Mtb). Blood monocytes (Mos) represent an important source of DCs during chronic infections; consequently, the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated whether the CD16(+)/CD16(-) Mo ratio could be associated with the impaired Mo differentiation into DCs found in TB patients.

Sex, ethnicity, and slow acetylator profile are the major causes of hepatotoxicity induced by antituberculosis drugs.

Background And Aim: Treatment with antituberculosis (TB) drugs produces liver damage in a large proportion of patients. Isoniazid, an antibacterial drug, is primarily responsible for this hepatotoxicity. Several polymorphisms of the N-acetyltransferase 2 (NAT-2) and cytochrome P450 2E1 enzymes, which are involved in the metabolism of isoniazid, may be directly associated with the development of hepatotoxicity.

Phosphorylation of mitogen-activated protein kinases contributes to interferon γ production in response to Mycobacterium tuberculosis.

Immune control of Mycobacterium tuberculosis depends on interferon γ (IFN-γ)-producing CD4(+) lymphocytes. Previous studies have shown that T cells from patients with tuberculosis produce less IFN-γ, compared with healthy donors, in response to mycobacterial antigens, although IFN-γ responses to mitogens are preserved. In this work, we found that M.

The distribution of allelic and genotypic frequencies of N-Acetyltransferase-2 variants in an Argentine population.

Introduction: Arylamine N-acetyltransferase-2 (NAT-2) is a key human enzyme in drug detoxification and elimination. Mutations in NAT-2 affect the activity of anti-tuberculosis drugs and result in three different phenotypes: rapid (RA), intermediate (IA) and slow acetylators (SA).

Methodology: The allelic, genotypic and phenotypic frequencies of NAT-2 were studied in 185 patients from Buenos Aires by restriction fragment length polymorphism.

ICOS, SLAM and PD-1 expression and regulation on T lymphocytes reflect the immune dysregulation in patients with HIV-related illness with pulmonary tuberculosis.

Background: Tuberculosis (TB) continues to be the most frequent cause of illness and death from an infectious agent globally, and its interaction with HIV is having devastating effects. To investigate how HIV alters the immune response to Mycobacterium tuberculosis (Mtb), we assessed basal and Mtb-induced proliferation, cytokine production, and expression of signalling lymphocytic activation molecule (SLAM), inducible costimulator (ICOS) and programmed death-1 (PD-1) on T lymphocytes from HIV-positive individuals coinfected with TB, HIV-positive subjects, TB patients and healthy donors (HD).

Findings: HIV-TB patients showed increased ICOS, SLAM and PD-1 basal levels on T lymphocytes, whereas HIV-positive individuals displayed elevated levels of SLAM and PD-1, TB patients high levels of SLAM, and HD low levels of the three proteins.

IL-17 and IFN-γ expression in lymphocytes from patients with active tuberculosis correlates with the severity of the disease.

Th1 lymphocytes are crucial in the immune response against Mycobacterium tuberculosis. Nevertheless, IFN-γ alone is not sufficient in the complete eradication of the bacteria, suggesting that other cytokines might be required for pathogen removal. Th17 cells have been associated with M.

CD137 differentially regulates innate and adaptive immunity against Mycobacterium tuberculosis.

Protective immunity against Mycobacterium tuberculosis is primarily mediated by the interaction of antigen-specific T cells and antigen presenting cells, which often depends on the interplay of cytokines produced by these cells. Costimulatory signals represent a complex network of receptor-ligand interactions that qualitatively and quantitatively influence immune responses. Thus, here we investigated the function of CD137 and CD137L, molecules known to have a central role in immune regulation, during human tuberculosis (TB).

Paradoxical role of CD16+CCR2+CCR5+ monocytes in tuberculosis: efficient APC in pleural effusion but also mark disease severity in blood.

The role of CD16(-) and CD16(+) Mo subsets in human TB remains unknown. Our aim was to characterize Mo subsets from TB patients and to assess whether the inflammatory milieu from TB pleurisy modulate their phenotype and recruitment. We found an expansion of peripheral CD16(+) Mo that correlated with disease severity and with TNF-α plasma levels.

Role played by the programmed death-1-programmed death ligand pathway during innate immunity against Mycobacterium tuberculosis.

Tuberculous pleurisy allows the study of specific cells at the site of Mycobacterium tuberculosis infection. Among pleural lymphocytes, natural killer (NK) cells are a major source of interferon gamma (IFN-gamma), and their functions are regulated by activating and inhibitory receptors. Programmed death-1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) are recognized inhibitory receptors in adaptive immunity, but their role during innate immunity remains poorly understood.

Mycobacterium tuberculosis impairs dendritic cell response by altering CD1b, DC-SIGN and MR profile.

During a chronic infection such as tuberculosis, the pool of tissue dendritic cells (DC) must be renewed by recruitment of both circulating DC progenitors and monocytes (Mo). However, the microenvironment of the inflammatory site affects Mo differentiation. As DC are critical for initiating a Mycobacterium tuberculosis-specific T-cell response, we argue that interference of M.

NK cells from tuberculous pleurisy express high ICAM-1 levels and exert stimulatory effect on local T cells.

Tuberculous pleurisy, one of the most common manifestations of extrapulmonary tuberculosis, is characterized by a T-cell-mediated hypersensitivity reaction along with a Th1 immune profile. In this study, we investigated functional cross-talk among T and NK cells in human tuberculous pleurisy. We found that endogenously activated pleural fluid-derived NK cells express high ICAM-1 levels and induce T-cell activation ex vivo through ICAM-1.

Secretory leukocyte protease inhibitor: a secreted pattern recognition receptor for mycobacteria.

Rationale: Human secretory leukocyte protease inhibitor (SLPI) displays bactericidal activity against pathogens such as Escherichia coli and Streptococcus. Furthermore, it has been reported that murine SLPI shows potent antimycobacterial activity.

Objectives: The aim of the present study was to investigate whether human recombinant SLPI not only kills mycobacteria but also acts as a pattern recognition receptor for the host immune system.

Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis.

Protective immunity against Mycobacterium tuberculosis requires the generation of cell-mediated immunity. We investigated the expression and role of programmed death 1 (PD-1) and its ligands, molecules known to modulate T cell activation, in the regulation of IFN-gamma production and lytic degranulation during human tuberculosis. We demonstrated that specific Ag-stimulation increased CD3+PD-1+ lymphocytes in peripheral blood and pleural fluid from tuberculosis patients in direct correlation with IFN-gamma production from these individuals.

Cross-talk between CD31 and the signaling lymphocytic activation molecule-associated protein during interferon- gamma production against Mycobacterium tuberculosis.

Effective host defense against tuberculosis requires Th1 cytokine responses. We studied the regulation of interferon (IFN)- gamma production during tuberculosis by investigating the role of CD31, a receptor that attenuates T cell receptor signals. After antigen stimulation, CD3(+)CD31(+) blood lymphocytes decreased in healthy donors and in tuberculosis patients with robust Th1 responses to Mycobacterium tuberculosis and IFN- gamma was secreted only by CD31(-) T cells.

Mycobacterium tuberculosis-induced gamma interferon production by natural killer cells requires cross talk with antigen-presenting cells involving Toll-like receptors 2 and 4 and the mannose receptor in tuberculous pleurisy.

Tuberculous pleurisy allows the study of human cells at the site of active Mycobacterium tuberculosis infection. In this study, we found that among pleural fluid (PF) lymphocytes, natural killer (NK) cells are a major source of early gamma interferon (IFN-gamma) upon M. tuberculosis stimulation, leading us to investigate the mechanisms and molecules involved in this process.