ABSTRACT
The effects of a fluroquinolone levofloxacin on apoptosis of peripheral blood lymphocytes from patients with infiltrative pulmonary tuberculosis were studied in vitro. It was found that levofloxacin stimulated apoptotic cell death in tuberculosis. Addition of levofloxacin to cell suspension from patients with drug-susceptible form of tuberculosis led to an increase in the number of CD95+ and AnnV+ lymphocytes. In patients with drug-resistant form of tuberculosis, only the number of apoptotic lymphocytes, but not the count of CD95+ cells increased under these conditions.
Subject(s)
Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Levofloxacin/pharmacology , Adult , Apoptosis/drug effects , Cells, Cultured , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/pathogenicity , Tuberculosis, Pulmonary , fas Receptor/metabolismABSTRACT
The effects levofloxacin (fluoroquinolone) and vaccinal BCG strain on cytokine production by blood mononuclear leukocytes was studied in patients with infiltrative pulmonary tuberculosis. Combined treatment with levofloxacin and vaccinal BCG strain suppressed the production of TNFα in drug-resistant pulmonary tuberculosis and production of IL-12 and IFNγ in drug-sensitive tuberculosis.
Subject(s)
Anti-Bacterial Agents/pharmacology , BCG Vaccine/pharmacology , Leukocytes, Mononuclear/drug effects , Levofloxacin/pharmacology , Tuberculosis, Pulmonary/immunology , Adult , Case-Control Studies , Drug Combinations , Drug Resistance, Multiple, Bacterial , Female , Humans , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Interleukin-12/biosynthesis , Interleukin-12/immunology , Interleukin-2/biosynthesis , Interleukin-2/immunology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/microbiology , Male , Middle Aged , Mycobacterium bovis/cytology , Mycobacterium bovis/immunology , Mycobacterium tuberculosis/cytology , Mycobacterium tuberculosis/immunology , Mycobacterium tuberculosis/pathogenicity , Primary Cell Culture , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/pathology , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/immunologyABSTRACT
The study of subpopulation structure of IFNγ-producing T cells in patients with pulmonary tuberculosis revealed a decrease in the number of CD3+ IFNγ+ cells against the background of significantly increased IFNγ secretion in vitro irrespective of the clinical form of the disease and drug sensitivity of M. tuberculosis, most strongly expressed in case of the disseminated tuberculosis. In patients with infiltrative drug-sensitive and drug-resistant pulmonary tuberculosis, increased number of Th1/Th17 lymphocytes (CD4+ IFNγ+IL-17A+) and, conversely, decreased number of blood γδT cells was detected.
Subject(s)
Cell Lineage/immunology , Interferon-gamma/immunology , Th1 Cells/immunology , Th17 Cells/immunology , Tuberculosis, Multidrug-Resistant/immunology , Tuberculosis, Pulmonary/immunology , Adult , Antitubercular Agents/therapeutic use , CD4 Antigens/genetics , CD4 Antigens/immunology , Case-Control Studies , Female , Gene Expression , Humans , Immunophenotyping , Interferon-gamma/genetics , Interleukin-17/genetics , Interleukin-17/immunology , Lymphocyte Count , Male , Middle Aged , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/growth & development , Mycobacterium tuberculosis/pathogenicity , Primary Cell Culture , Receptors, Antigen, T-Cell, gamma-delta/genetics , Receptors, Antigen, T-Cell, gamma-delta/immunology , Th1 Cells/drug effects , Th1 Cells/microbiology , Th17 Cells/drug effects , Th17 Cells/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/genetics , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/genetics , Tuberculosis, Pulmonary/microbiologyABSTRACT
In patients with infiltrative pulmonary tuberculosis, the increase in IL-6 secretion, the decrease in TGFß production (in case of drug resistance of the causative agent), and unchanged level of IL-1ß secretion by mononuclear leukocytes in vitro were associated with increased number of CD4(+)CD161(+)IL-17A(+) Th17 lymphocytes in the peripheral blood. In patients with disseminated drug-resistant pulmonary tuberculosis, TGFß hyperproduction promoted differentiation of CD4(+)CD25(+)FoxP3(+) Treg lymphocytes with immunosuppressive activity.
Subject(s)
Cell Differentiation/immunology , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Tuberculosis, Pulmonary/immunology , Adult , CD4 Antigens/metabolism , Female , Forkhead Transcription Factors/metabolism , Humans , Interleukin-2 Receptor alpha Subunit/metabolism , Male , Middle Aged , NK Cell Lectin-Like Receptor Subfamily B/metabolism , Statistics, Nonparametric , T-Lymphocytes, Regulatory/metabolism , Th17 Cells/metabolism , Transforming Growth Factor beta/immunology , Tuberculosis, Pulmonary/bloodABSTRACT
Homeostasis of subpopulations Th17- and Treg-lymphocytes plays an important role in a holistic and coordinated process of eradication of pathogens and preventing the spread of infection in the body. Study of molecular mechanisms controlling the balance of these cells in the formation of immune deviation in the pathogenesis of infection are particularly relevant. The article presents the results of a study of mRNA expression of transcription factors Th17- and Treg-lymphocytes--RORC2 and FoxP3, respectively, as well as the presence of these cells in peripheral blood in infectious disease (based on an example of infection caused by Mycobacterium tuberculosis). It was established that during the infiltrative (regardless of drug susceptibility testing) and disseminated drug-susceptible pulmonary tuberculosis accompanied by Th17-polarized differentiation of T-lymphocytes, as evidenced by the increased number of CD4+CD161+IL17A+ cells in the blood in association with increased mRNA expression of the transcription factor RORC2 in lymphocytes. In disseminated drug-resistant pulmonary tuberculosis T-lymphocyte differentiation is carried out mainly in the direction of immunosuppressive Treg-cells, as evidenced by the increase in their number in the blood in association with elevated levels of mRNA expression of the transcription factor FoxP3 in lymphocytes.
Subject(s)
Forkhead Transcription Factors/genetics , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , RNA, Messenger/genetics , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Tuberculosis, Multidrug-Resistant/immunology , Tuberculosis, Pulmonary/immunology , Adult , Antitubercular Agents/therapeutic use , Case-Control Studies , Cell Differentiation , Disease Progression , Female , Forkhead Transcription Factors/immunology , Gene Expression Regulation/immunology , Humans , Immunity, Innate , Male , Microbial Sensitivity Tests , Middle Aged , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/immunology , Nuclear Receptor Subfamily 1, Group F, Member 3/immunology , Protein Isoforms/genetics , Protein Isoforms/immunology , RNA, Messenger/immunology , T-Lymphocytes, Regulatory/microbiology , T-Lymphocytes, Regulatory/pathology , Th17 Cells/microbiology , Th17 Cells/pathology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Multidrug-Resistant/pathology , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/pathologyABSTRACT
Increased content of CD4(+)CD161(+)IL-17A(+) Th17 lymphocytes in the peripheral blood was found in patients with pulmonary tuberculosis irrespective of the clinical form (infiltrative, disseminated) and variant of the disease (drug-sensitive, drug-resistant). The elevated content of Th17 cells in pulmonary tuberculosis is associated with hypersecretion of Th17-associated cytokines IL-17A and IL-22 in vitro that was most pronounced (in case of IL-17A) in patients with disseminated pulmonary tuberculosis.
Subject(s)
Interleukin-17/metabolism , Interleukins/metabolism , Mycobacterium tuberculosis/immunology , Th17 Cells/immunology , Tuberculosis, Pulmonary/immunology , Adult , CD4 Antigens/metabolism , Cells, Cultured , Female , Humans , Male , Middle Aged , NK Cell Lectin-Like Receptor Subfamily B/metabolism , Young Adult , Interleukin-22ABSTRACT
The analysis of current views on functional and immunoregulatory role of T-lymphocytes-helpers of type 17 (Th17) in anti-infectious immune response is presented, in particular, in the development of protective immune reactions to intracellular pathogens. Particular attention is paid to participation of these lymphocytes and cytokines produced by them in immune response to Mycobacterium tuberculosis invasion. The molecular mechanisms, underlying the predominant development of Th17-lymphocytes and/or regulatory T-cells (Treg), are studied, with evaluation of interconnection of these cell subpopulations in formation of immune imbalance in infectious pathology.
Subject(s)
Cytokines/immunology , Immunity, Innate , Th17 Cells/immunology , Tuberculosis/immunology , Cytokines/biosynthesis , Humans , Mycobacterium tuberculosis/immunology , T-Lymphocytes, Regulatory/immunology , Tuberculosis/microbiology , Tuberculosis/therapyABSTRACT
The influence of the main antituberculosis drugs (isoniazid, rifampicin, ethambutol) on in vitro apoptosis of peripheral blood lymphocytes from patients with pulmonary tuberculosis was researched. It was shown that all the investigated drugs induced apoptotic death of the lymphocytes in vitro, that could result in disturbance of antigen-specific response formation in pulmonary tuberculosis.
Subject(s)
Antitubercular Agents/adverse effects , Apoptosis/drug effects , Ethambutol/adverse effects , Isoniazid/adverse effects , Lymphocytes/drug effects , Rifampin/adverse effects , Humans , Tuberculosis, Pulmonary/drug therapyABSTRACT
Modern immunological and molecular genetic studies showed that tuberculosis is accompanied by an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes. T allele and homozygous TT genotype of T-330G polymorphism in the IL2 gene, T allele and TT genotype of C-590T polymorphism in the IL4 gene, and CC genotype of A-1188C polymorphism in the IL12B gene are immunogenetic factors that have protective activity against susceptibility to pulmonary tuberculosis. Susceptibility to tuberculous infection is associated with A1A2 genotype of the polymorphic region +3953 A1/A2 in the IL1B gene; G allele and TG and GG genotypes of T-330G polymorphism in the IL2 gene; C allele and CC and CT genotypes of C-590T polymorphism in the IL4 gene; and AC genotype of the polymorphic region A-1188C in the IL12 gene.
