- Authors: Lorenzzo Lyrio Stringari, Luciana Polaco Covre, Flávia Dias Coelho da Silva, Vivian Leite de Oliveira, Maria Carolina Campana, David Jamil Hadad, Moisés Palaci, Padmini Salgame, Reynaldo Dietze, Daniel Cláudio de Oliveira Gomes, Rodrigo Ribeiro-Rodrigues
- Publication Year: 2021
- Journal: Plos Neglected Tropical Diseases, 15(7), art e0009605
- Link: https://doi.org/10.1371/journal.pntd.0009605
ABSTRACT
‘Background:’
Regulatory T cells (Tregs) play a critical role during Mycobacterium tuberculosis (Mtb) infection, modulating host responses while neutralizing excessive inflammation. However, their impact on regulating host protective immunity is not completely understood. Here, we demonstrate that Treg cells abrogate the in vitro microbicidal activity against Mtb.
‘Methods:’
We evaluated the in vitro microbicidal activity of peripheral blood mononuclear cells (PBMCs) from patients with active tuberculosis (TB), individuals with latent tuberculosis infection (LTBI, TST+/IGRA+) and healthy control (HC, TST-/IGRA-) volunteers. PBMCs, depleted or not of CD4+CD25+ T-cells, were analyzed to determine frequency and influence on microbicidal activity during in vitro Mtb infection with four clinical isolates (S1, S5, R3, and R6) and one reference strain (H37Rv).
‘Results:’
The frequency of CD4+CD25highFoxP3+ cells were significantly higher in Mtb infected whole blood cultures from both TB patients and LTBI individuals when compared to HC. Data from CD4+CD25+ T-cells depletion demonstrate that increase of CD4+CD25highFoxP3+ is associated with an impairment of Th-1 responses and a diminished in vitro microbicidal activity of LTBI and TB groups.
‘Conclusions:’
Tregs restrict host anti-mycobacterial immunity during active disease and latent infection and thereby may contribute to both disease progression and pathogen persistence.
AUTHOR SUMMARY
Our immune system has an enormous capacity of recognizing and responding to foreign antigens and, likewise, presents an extremely efficient mechanism of controlling these responses. Here, we investigated how a specific cell type with regulatory abilities can interfere in the immunological response against tuberculosis bacillus. For this, we used blood samples from individuals sensitized with the bacillus and patients with active pulmonary tuberculosis to understand how these cells act and their impact on the host/parasite relationship in the development of the disease. We could observe the negative impact that such regulatory cells cause during the immune response against Mycobacterium tuberculosis, decreasing the control/elimination of the bacillus in asymptomatic individuals and patients with tuberculosis. We also observed a recovery in the immune response when Treg cells were removed during in vitro challenge, restoring the capacity of Mtb clearance. Thus, these regulatory cells, when present, may represent a possible facilitator of the asymptomatic permanence of the bacillus, or even of the development of the disease itself. These data allowed us to see latency and tuberculosis from a new angle and thus postulate new approaches to fight tuberculosis.
KEYWORDS
Mycobacterium tuberculosis; Tuberculosis; Regulatory T cells; Blood; Immune response; Extensively drug-resistant tuberculosis; Sputum; Tuberculin.