Central Tuberculosis Research Institute

Moscow, Russia

Central Tuberculosis Research Institute

Moscow, Russia

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Nikitina I.Y.,Central Tuberculosis Research Institute | Kondratuk N.A.,Central Tuberculosis Research Institute | Kosmiadi G.A.,Central Tuberculosis Research Institute | Amansahedov R.B.,Central Tuberculosis Research Institute | And 4 more authors.
PLoS ONE | Year: 2012

Background: Effector CD4 T cells represent a key component of the host's anti-tuberculosis immune defense. Successful differentiation and functioning of effector lymphocytes protects the host against severe M. tuberculosis (Mtb) infection. On the other hand, effector T cell differentiation depends on disease severity/activity, as T cell responses are driven by antigenic and inflammatory stimuli released during infection. Thus, tuberculosis (TB) progression and the degree of effector CD4 T cell differentiation are interrelated, but the relationships are complex and not well understood. We have analyzed an association between the degree of Mtb-specific CD4 T cell differentiation and severity/activity of pulmonary TB infection. Methodology/Principal Findings: The degree of CD4 T cell differentiation was assessed by measuring the percentages of highly differentiated CD27 low cells within a population of Mtb- specific CD4 T lymphocytes ("CD27 lowIFN-γ +" cells). The percentages of CD27 lowIFN-γ+ cells were low in healthy donors (median, 33.1%) and TB contacts (21.8%) but increased in TB patients (47.3%, p<0.0005). Within the group of patients, the percentages of CD27 lowIFN-γ + cells were uniformly high in the lungs (>76%), but varied in blood (12-92%). The major correlate for the accumulation of CD27 lowIFN-γ + cells in blood was lung destruction (r = 0.65, p = 2.7×10 -7). A cutoff of 47% of CD27 lowIFN-γ + cells discriminated patients with high and low degree of lung destruction (sensitivity 89%, specificity 74%); a decline in CD27 lowIFN-γ +cells following TB therapy correlated with repair and/or reduction of lung destruction (p<0.01). Conclusions: Highly differentiated CD27 low Mtb-specific (CD27 lowIFN-γ +) CD4 T cells accumulate in the lungs and circulate in the blood of patients with active pulmonary TB. Accumulation of CD27 lowIFN-γ + cells in the blood is associated with lung destruction. The findings indicate that there is no deficiency in CD4 T cell differentiation during TB; evaluation of CD27 lowIFN-γ + cells provides a valuable means to assess TB activity, lung destruction, and tissue repair following TB therapy. © 2012 Nikitina et al.


Lyadova I.V.,Central Tuberculosis Research Institute | Panteleev A.V.,Central Tuberculosis Research Institute
Mediators of Inflammation | Year: 2015

The outcome of Mycobacterium tuberculosis (Mtb) infection ranges from a complete pathogen clearance through asymptomatic latent infection (LTBI) to active tuberculosis (TB) disease. It is now understood that LTBI and active TB represent a continuous spectrum of states with different degrees of pathogen "activity," host pathology, and immune reactivity. Therefore, it is important to differentiate LTBI and active TB and identify active TB stages. CD4+ T cells play critical role during Mtb infection by mediating protection, contributing to inflammation, and regulating immune response. Th1 and Th17 cells are the main effector CD4+ T cells during TB. Th1 cells have been shown to contribute to TB protection by secreting IFN-γ and activating antimycobacterial action in macrophages. Th17 induce neutrophilic inflammation, mediate tissue damage, and thus have been implicated in TB pathology. In recent years new findings have accumulated that alter our view on the role of Th1 and Th17 cells during Mtb infection. This review discusses these new results and how they can be implemented for TB diagnosis and monitoring. © 2015 I. V. Lyadova and A. V. Panteleev.


Sotnikov D.V.,RAS A.N. Bach Institute of Biochemistry | Zherdev A.V.,RAS A.N. Bach Institute of Biochemistry | Avdienko V.G.,Central Tuberculosis Research Institute | Dzantiev B.B.,RAS A.N. Bach Institute of Biochemistry
Applied Biochemistry and Microbiology | Year: 2015

A new immunochromatographic assay was developed for serodiagnosis of tuberculosis based on the interaction of specific anti-Mycobacterium tuberculosis immunoglobulins that are present in the blood serum with a label-antigen conjugate followed by the binding of the resulting complex to the Staphylococcus aureus protein A immobilized on a test strip. Unlike the conventional technique, in which all immunoglobulins that are present in the sample react with a label-immunoglobulin-binding protein conjugate, the new technique eliminates the binding of blood serum immunoglobulins, which are non-specific to Mycobacterium tuberculosis, to the label, and then specific antibodies involved in the labeled complex bind to the immobilized antigen. The new assay was implemented using the recombinant 38-kDa (Rv0934) protein of M. tuberculosis as the antigen and colloidal gold as the label. It was experimentally shown that the new assay allows for an increase in the percentage of the detection of seropositive serum samples with low concentrations of specific antibodies against the causative agent of tuberculosis. © 2015, Pleiades Publishing, Inc.


Day T.A.,Max Planck Institute for Infection Biology | Day T.A.,Seattle Biomedical Research Institute | Koch M.,Max Planck Institute for Infection Biology | Koch M.,Bayer AG | And 13 more authors.
European Journal of Immunology | Year: 2010

Tuberculosis causes 2 million deaths per year, yet in most cases the immune response successfully contains the infection and prevents disease outbreak. Induced lymphoid structures associatedwith pulmonary granuloma are observed during tuberculosis in both humans and mice and could orchestrate host defense. To investigate whether granuloma perform lymphoid functions, mice lacking secondary lymphoid organs (SLO) were infected with Mycobacterium tuberculosis (MTB). As in WT mice, granuloma developed, exponential growth of MTB was controlled, and antigen-specific T-cell responses including memory T cells were generated in the absence of SLO. Moreover, adoptively transferred T cellswere primed locally in lungs in a granuloma-dependent manner. T-cell activation was delayed in the absence of SLO, but resulted in a normal development program including protective subsets and functional recall responses that protected mice against secondary MTB infection. Our data demonstrate that protective immune responses can be generated independently of SLO during MTB infection and implicate local pulmonary T-cell priming as a mechanism contributing to host defense. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.


Duque-Correa M.A.,Max Planck Institute for Infection Biology | Kuhl A.A.,Max Planck Institute for Infection Biology | Rodriguez P.C.,Charité - Medical University of Berlin | Zedler U.,Max Planck Institute for Infection Biology | And 10 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Lung granulomas develop upon Mycobacterium tuberculosis (Mtb) infection as a hallmark of human tuberculosis (TB). They are structured aggregates consisting mainly of Mtb-infected and -unin-fected macrophages and Mtb-specific T cells. The production of NO by granuloma macrophages expressing nitric oxide synthase-2 (NOS2) via L-arginine and oxygen is a key protective mechanism against mycobacteria. Despite this protection, TB granulomas are often hypoxic, and bacterial killing via NOS2 in these conditions is likely suboptimal. Arginase-1 (Arg1) also metabolizes L-arginine but does not require oxygen as a substrate and has been shown to regulate NOS2 via substrate competition. However, in other infectious diseases in which granulomas occur, such as leishmaniasis and schistosomiasis, Arg1 plays additional roles such as T-cell regulation and tissue repair that are independent of NOS2 suppression. To address whether Arg1 could perform similar functions in hypoxic regions of TB granulomas, we used a TB murine granu-loma model in which NOS2 is absent. Abrogation of Arg1 expression in macrophages in this setting resulted in exacerbated lung granuloma pathology and bacterial burden. Arg1 expression in hyp-oxic granuloma regions correlated with decreased T-cell proliferation, suggesting that Arg1 regulation of T-cell immunity is involved in disease control. Our data argue that Arg1 plays a central role in the control of TB when NOS2 is rendered ineffective by hypoxia.


Vladimirovna I.L.,Central Tuberculosis Research Institute | Sosunova E.,Central Tuberculosis Research Institute | Nikolaev A.,Central Tuberculosis Research Institute | Nenasheva T.,Central Tuberculosis Research Institute
Journal of Immunology Research | Year: 2016

To protect host against immune-mediated damage, immune responses are tightly regulated. The regulation of immune responses is mediated by various populations of mature immune cells, such as T regulatory cells and B regulatory cells, but also by immature cells of different origins. In this review, we discuss regulatory properties and mechanisms whereby two distinct populations of immature cells, mesenchymal stem cells, and myeloid derived suppressor cells mediate immune regulation, focusing on their similarities, discrepancies, and potential clinical applications. © 2016 Irina Lyadova Vladimirovna et al.


PubMed | Central Tuberculosis Research Institute
Type: | Journal: Journal of immunology research | Year: 2017

IFN-


PubMed | Central Tuberculosis Research Institute
Type: | Journal: Mediators of inflammation | Year: 2015

The outcome of Mycobacterium tuberculosis (Mtb) infection ranges from a complete pathogen clearance through asymptomatic latent infection (LTBI) to active tuberculosis (TB) disease. It is now understood that LTBI and active TB represent a continuous spectrum of states with different degrees of pathogen activity, host pathology, and immune reactivity. Therefore, it is important to differentiate LTBI and active TB and identify active TB stages. CD4(+) T cells play critical role during Mtb infection by mediating protection, contributing to inflammation, and regulating immune response. Th1 and Th17 cells are the main effector CD4(+) T cells during TB. Th1 cells have been shown to contribute to TB protection by secreting IFN- and activating antimycobacterial action in macrophages. Th17 induce neutrophilic inflammation, mediate tissue damage, and thus have been implicated in TB pathology. In recent years new findings have accumulated that alter our view on the role of Th1 and Th17 cells during Mtb infection. This review discusses these new results and how they can be implemented for TB diagnosis and monitoring.


PubMed | Central Tuberculosis Research Institute
Type: | Journal: Journal of immunology research | Year: 2016

To protect host against immune-mediated damage, immune responses are tightly regulated. The regulation of immune responses is mediated by various populations of mature immune cells, such as T regulatory cells and B regulatory cells, but also by immature cells of different origins. In this review, we discuss regulatory properties and mechanisms whereby two distinct populations of immature cells, mesenchymal stem cells, and myeloid derived suppressor cells mediate immune regulation, focusing on their similarities, discrepancies, and potential clinical applications.


PubMed | Central Tuberculosis Research Institute
Type: Journal Article | Journal: PloS one | Year: 2012

Effector CD4 T cells represent a key component of the hosts anti-tuberculosis immune defense. Successful differentiation and functioning of effector lymphocytes protects the host against severe M. tuberculosis (Mtb) infection. On the other hand, effector T cell differentiation depends on disease severity/activity, as T cell responses are driven by antigenic and inflammatory stimuli released during infection. Thus, tuberculosis (TB) progression and the degree of effector CD4 T cell differentiation are interrelated, but the relationships are complex and not well understood. We have analyzed an association between the degree of Mtb-specific CD4 T cell differentiation and severity/activity of pulmonary TB infection.The degree of CD4 T cell differentiation was assessed by measuring the percentages of highly differentiated CD27(low) cells within a population of Mtb- specific CD4 T lymphocytes (CD27(low)IFN-(+) cells). The percentages of CD27(low)IFN-+ cells were low in healthy donors (median, 33.1%) and TB contacts (21.8%) but increased in TB patients (47.3%, p<0.0005). Within the group of patients, the percentages of CD27(low)IFN-(+) cells were uniformly high in the lungs (>76%), but varied in blood (12-92%). The major correlate for the accumulation of CD27(low)IFN-(+) cells in blood was lung destruction (r = 0.65, p = 2.7 10(-7)). A cutoff of 47% of CD27(low)IFN-(+) cells discriminated patients with high and low degree of lung destruction (sensitivity 89%, specificity 74%); a decline in CD27(low)IFN-(+)cells following TB therapy correlated with repair and/or reduction of lung destruction (p<0.01).Highly differentiated CD27(low) Mtb-specific (CD27(low)IFN-(+)) CD4 T cells accumulate in the lungs and circulate in the blood of patients with active pulmonary TB. Accumulation of CD27(low)IFN-(+) cells in the blood is associated with lung destruction. The findings indicate that there is no deficiency in CD4 T cell differentiation during TB; evaluation of CD27(low)IFN-(+) cells provides a valuable means to assess TB activity, lung destruction, and tissue repair following TB therapy.

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