GHTM

Global Health and Tropical Medicine

  • GHTM
    • About GHTM
    • Governance
    • Impact
    • Members
      • Population health, policies and services
        • PPS PhD members
        • PPS non PhD members
      • TB, HIV and opportunistic diseases and pathogens
        • THOP PhD members
        • THOP non PhD members
      • Vector-borne diseases
        • VBD PhD members
        • VBD non PhD members
      • Individual Health Care
        • IHC PhD members
        • IHC non PhD members
      • Tech & Admin support
    • Scientific Advisory Board
  • Research
    • Cross-cutting issues
      • Global Pathogen Dispersion and Population Mobility
      • Drug Discovery and Drug Resistance
      • Diagnostics
      • Public Health Information
      • Fair Research Partnerships
    • Research Groups
      • PPS – Population health, policies and services
      • THOP – TB, HIV and opportunistic diseases and pathogens
      • VBD – Vector borne diseases
      • IHC – Individual health care
    • Research in numbers
      • 2023
      • 2022
      • 2021
      • 2020
      • 2019
      • 2018
      • 2017
    • Projects
      • Ongoing Projects
      • Completed Projects
  • Outreach
    • Events
    • News
    • Policy Support & Community Outreach
  • Publications
    • 2024
    • 2023
    • 2022
    • 2021
    • 2020
    • 2019
    • 2018
    • 2017
    • 2016
    • 2015
  • Capacity Building
    • Education
      • Master Theses
      • PhD Theses
    • International
  • Infrastructures
  • Networks & Partnerships
  • Reports
    • GHTM
    • Scientific Advisory Board
    • FCT
Home / Publications / Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis

Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis

  • 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.

Share this:

  • Click to share on Facebook (Opens in new window) Facebook
  • Click to share on X (Opens in new window) X
  • Click to share on LinkedIn (Opens in new window) LinkedIn
  • Click to share on Pinterest (Opens in new window) Pinterest
  • Click to share on WhatsApp (Opens in new window) WhatsApp
  • Click to print (Opens in new window) Print

About GHTM

GHTM is a R&D Unit that brings together researchers with a track record in Tropical Medicine and International & Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

Contacts

Rua da Junqueira, 100
1349-008 Lisboa
Portugal

+351 213 652 600

  • E-mail
  • Facebook
  • LinkedIn
  • Twitter
  • YouTube

Map

  • Events
  • Research Groups
  • Cross-cutting issues
© Copyright 2025 IHMT-UNL All Rights Reserved.
  • Universidade Nova de Lisboa
  • Fundação para a Ciência e a Tecnologia

    UIDB/04413/2020
    UIDP/04413/2020

We use cookies to ensure that we give you the best experience on our website. If you continue to use this site we will assume that you are happy with it.Ok