Increase of cd4+cd25highfoxp3+ cells impairs in vitro human microbicidal activity against mycobacterium tuberculosis during latent and acute pulmonary tuberculosis

Autor: Lorenzzo Lyrio Stringari, David Jamil Hadad, Padmini Salgame, Rodrigo Ribeiro-Rodrigues, Reynaldo Dietze, Vivian L. de Oliveira, Daniel Cláudio de Oliveira Gomes, Flávia Dias Coelho da Silva, Luciana Polaco Covre, Maria Carolina Campana, Moises Palaci
Přispěvatelé: Instituto de Higiene e Medicina Tropical (IHMT), Individual Health Care (IHC), Global Health and Tropical Medicine (GHTM)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Bacterial Diseases
Physiology
Extensively Drug-Resistant Tuberculosis
RC955-962
T-Lymphocytes
Regulatory
Medical Conditions
Arctic medicine. Tropical medicine
Cellular types
Medicine and Health Sciences
IL-2 receptor
Immune Response
Latent tuberculosis
biology
Immune cells
Forkhead Transcription Factors
Regulatory T cells
Microbiologia Médica
Body Fluids
Actinobacteria
Blood
Infectious Diseases
CD4 Antigens
White blood cells
Anatomy
Public aspects of medicine
RA1-1270
Research Article
Blood Bactericidal Activity
Cell biology
Blood cells
Tuberculosis
030106 microbiology
Immunology
T cells
chemical and pharmacologic phenomena
Peripheral blood mononuclear cell
Mycobacterium tuberculosis
03 medical and health sciences
Immune system
SDG 3 - Good Health and Well-being
Immunity
Latent Tuberculosis
medicine
Humans
Tuberculosis
Pulmonary
Bacteria
business.industry
Interleukin-2 Receptor alpha Subunit
Organisms
Sputum
Public Health
Environmental and Occupational Health
Extensively drug-resistant tuberculosis
Biology and Life Sciences
medicine.disease
biology.organism_classification
Tropical Diseases
bacterial infections and mycoses
Mucus
030104 developmental biology
Animal cells
Case-Control Studies
business
Zdroj: PLoS Neglected Tropical Diseases, Vol 15, Iss 7, p e0009605 (2021)
PLoS Neglected Tropical Diseases
Popis: 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.
Databáze: OpenAIRE
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