English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

To the Editor—CD4CD25FoxP3 regulatory T cells (Tregs) are critical for the maintenance of immune tolerance by suppressing immune cell functions. In the context of infection such as Mycobacterium tuberculosis, Tregs can also suppress efficient protective immune responses against the pathogen and its effective clearance [1]. Results from studies of patients with tuberculosis and experimental models have shown that Tregs are expanded and accumulated at the site of infection. These Tregs efficiently inhibit the arrival of effector T cells in the lungs, production of interferon (IFN)–c and cd T-cell responses to M. tuberculosis [2–4]. However, mechanisms underlying the expansion of Tregs are not clear. Periasamy et al [5] identified that Treg expansion by M. tuberculosis requires expression of the protein programmed death-1 (PD-1, CD279). Inhibition of PD-1 by blocking antibodies or small interfering RNA prevented the Treg expansion. However, the questions that remain unanswered are as follows: does M. tuberculosis trigger dynamic changes in the expression of signaling molecules on innate immune cells that, in turn, facilitate Treg expansion, and if so, which innate pattern recognition receptors are implicated in this process? Because Treg expansion in the periphery requires costimulatory signals and antigen presentation by antigen-presenting cells such as dendritic cells (DCs), we surmised that the Treg expansion observed by the Periasamy et al [5] might reflect the modulation of DCs by M. tuberculosis. After education by M. tuberculosis, these DCs then might provide signals for expansion of Tregs. To address our hypothesis, immature DCs were derived by culturing peripheral blood monocytes (isolated by using CD14 microbeads; Miltenyi Biotec) from healthy blood donors after ethical committee permission, in the presence of granulocyte microphage colonystimulating factor (GM-CSF; 1000 IU/10 cells) and IL-4 (500 IU/10 cells). The 5-day-old immature DCs (0.5x10/ml) were either cultured in the presence of cytokines alone or cytokines plus whole cell lysates (WCLs) of pathogenic M. tuberculosis H37Rv (5 microgram/mL) for 48 h. The DCs were washed thoroughly and were cocultured with 0.2 3 106 CD4 1 T cells at 1:10 ratio for 96 h. CD4 T cells were isolated by using CD4 microbeads. The DCs and CD4 T cells were from unrelated donors, and hence CD3 and CD28 stimulation was not provided. The frequency of CD4CD25FoxP3 Tregs was analyzed using flow cytometry (LSR II, BD Biosciences). Surface staining was performed with fluorochrome-conjugated monoclonal antibodies (MAbs) to CD4 and CD25 (BD Biosciences), and intracellular staining for FoxP3 was performed using fluorochrome-conjugated MAb to FoxP3 and kit from eBioscience. We found that M. tuberculosis–treated DCs significantly expand Tregs (3.5% 6 0.5% in control vs 6.6% 6 0.8% in M. tuberculosis–treated DCs; n 5 5; Figure 1A). The results suggest that the Treg expansion observed by Periasamy et al [5] was indeed attributable to modulation of DC (or innate immune cells in general) functions by M. tuberculosis.

Mycobacterium tuberculosis Promotes Regulatory T-Cell Expansion via Induction of Programmed Death-1 Ligand 1 (PD-L1, CD274) on Dendritic Cells