transforming-growth-factor-beta and Latent-Tuberculosis

Anti-inflammatory cytokines act as double edged swords- they can dampen inflammation but can also suppress immunity. The role played by these cytokines in latent TB infected (LTBI) subjects, with various grades of glucose intolerance was studied. Both serum levels and recall-secretion of IL-27, IL-10, IL-1Ra and TGF-β in Normal Glucose Tolerance (NGT), Pre-Diabetes (PDM), Newly diagnosed Diabetes (NDM) and Known Diabetes (KDM) subjects, both with and without LTBI (n = 382), were quantified by ELISA. All the subjects were screened for LTBI by QuantiFERON-TB Gold test. Serum levels of IL-27, IL-10 and IL-1Ra were significantly elevated in the LTB

Topics: Adult; Cholesterol; Cytokines; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Glucose Intolerance; Humans; Inflammation Mediators; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-27; Latent Tuberculosis; Middle Aged; Reproducibility of Results; Sensitivity and Specificity; Transforming Growth Factor beta

Type 2 diabetes mellitus (DM) is a risk factor for the development of active tuberculosis (TB), although its role in the TB-induced responses in latent TB (LTB) is not well understood. Since Th1, Th2, and Th17 responses are important in immunity to LTB, we postulated that coincident DM could alter the function of these CD4(+) T-cell subsets. To this end, we examined mycobacteria-induced immune responses in the whole blood of individuals with LTB-DM and compared them with responses of individuals without DM (LTB-NDM). T-cell responses from LTB-DM are characterized by diminished frequencies of mono- and dual-functional CD4(+) Th1, Th2, and Th17 cells at baseline and following stimulation with mycobacterial antigens-purified protein derivative, early secreted antigen-6, and culture filtrate protein-10. This modulation was at least partially dependent on IL-10 and TGF-β, since neutralization of either cytokine resulted in significantly increased frequencies of Th1 and Th2 cells but not Th17 cells in LTB-DM but not LTB individuals. LTB-DM is therefore characterized by diminished frequencies of Th1, Th2, and Th17 cells, indicating that DM alters the immune response in latent TB leading to a suboptimal induction of protective CD4(+) T-cell responses, thereby providing a potential mechanism for increased susceptibility to active disease.

Topics: Adult; Aged; Antibodies, Neutralizing; Antigens, Bacterial; Bacterial Proteins; Diabetes Mellitus, Type 2; Disease Susceptibility; Female; Humans; Interleukin-10; Latent Tuberculosis; Lymphocyte Activation; Male; Middle Aged; Th1 Cells; Th17 Cells; Th2 Cells; Transforming Growth Factor beta; Young Adult

Rheumatoid arthritis (RA) is an autoimmune disease characterised by the destruction of articular cartilage and bone damage. The chronic treatment of RA patients causes a higher susceptibility to infectious diseases such as tuberculosis (TB); one-third of the world's population is latently infected (LTBI) with Mycobacterium tuberculosis (Mtb). The tuberculin skin test is used to identify individuals LTBI, but many studies have shown that this test is not suitable for RA patients. The goal of this work was to test the specific cellular immune responses to the Mtb malate synthase (GlcB) and heat shock protein X (HspX) antigens of RA patients and to correlate those responses with LTBI status. The T-helper (Th)1, Th17 and Treg-specific immune responses to the GlcB and HspX Mtb antigens were analysed in RA patients candidates for tumour necrosis factor-α blocker treatment. Our results demonstrated that LTBI RA patients had Th1-specific immune responses to GlcB and HspX. Patients were followed up over two years and 14.3% developed active TB. After the development of active TB, RA patients had increased numbers of Th17 and Treg cells, similar to TB patients. These results demonstrate that a GlcB and HspX antigen assay can be used as a diagnostic test to identify LTBI RA patients.

Topics: Adult; Aged; Analysis of Variance; Antigens, Bacterial; Arthritis, Rheumatoid; Bacterial Proteins; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Humans; Immunity, Cellular; Interleukin-6; Latent Tuberculosis; Leukocytes, Mononuclear; Longitudinal Studies; Malate Synthase; Male; Middle Aged; Mycobacterium tuberculosis; T-Lymphocytes, Regulatory; Th1 Cells; Th17 Cells; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4+ T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored.. To determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells ex vivo and following TB - antigen or polyclonal stimulation in pulmonary TB (PTB; n = 30) and latent TB (LTB; n = 20) individuals, using the markers CXCR5, PD-1 and ICOS.. We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals. Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFNγ. This was not accompanied by diminished frequencies of activated or memory B cell subsets. Finally, the diminution in frequency of Tfh cells in PTB individuals was dependent on IL-10, CTLA-4 and PD-L1 in vitro.. Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets.

Topics: Antigens, Bacterial; CD3 Complex; CTLA-4 Antigen; Humans; Immunologic Memory; Inducible T-Cell Co-Stimulator Protein; Interleukin-10; Interleukins; Latent Tuberculosis; Lymphocyte Count; Plasma Cells; Programmed Cell Death 1 Receptor; T-Lymphocytes, Helper-Inducer; Transforming Growth Factor beta; Tuberculosis, Pulmonary