Evaluation of the effect of T regulatory cell depletion and donor BCG vaccination on Mycobacterium tuberculosis H37Ra infection using an in vitro model of human PBMC infection.
BCG Vaccine
/ immunology
Bacterial Load
Cytokines
/ immunology
Host-Pathogen Interactions
Humans
Immunity
Interferon-gamma
/ immunology
Interleukin-10
/ immunology
Interleukin-17
/ immunology
Interleukin-4
/ immunology
Interleukin-6
/ immunology
Leukocytes, Mononuclear
/ immunology
Mycobacterium tuberculosis
T-Lymphocytes, Regulatory
/ immunology
Tuberculosis
/ immunology
Tumor Necrosis Factor-alpha
/ immunology
Vaccination
Mtb
Mycobacterium
PBMC
T regulatory cells
immune responses
microbiology
Journal
Pathogens and disease
ISSN: 2049-632X
Titre abrégé: Pathog Dis
Pays: United States
ID NLM: 101595366
Informations de publication
Date de publication:
09 12 2020
09 12 2020
Historique:
received:
12
02
2020
accepted:
09
11
2020
entrez:
10
12
2020
pubmed:
11
12
2020
medline:
8
9
2021
Statut:
ppublish
Résumé
This study evaluated the effect of T regulatory cells (Treg cells) and the impact of BCG vaccination history of donors using an in vitro model of Mycobacterium tuberculosis H37Ra infection of peripheral blood mononuclear cells (PBMCs). PBMCs from donors with or without prior BCG vaccination were depleted of Treg cells (PBMCs-Tregs) or not depleted with Treg cells (PBMCs + Tregs) were infected up to 8 days with Mtb H37Ra. Cell aggregates were smaller in PBMCs-Tregs compared to PBMCs + Tregs at day 8 post-infection. Mtb CFUs were higher in the PBMCs-Tregs compared to PBMCs + Tregs at days 3, 5 and 8. The levels of IL-17, IFN-γ (at days 3 and 5), and TNF-α and IL-6 (at day 3) were lower in PBMCs-Tregs compared to PBMCs + Tregs. In contrast, the levels of IL-10 and IL-4 cytokines were higher at day 3 in PBMCs-Tregs compared to PBMCs + Tregs. BCG vaccination status of donors had no impact on the mycobacterial culture, level of cytokines and immune cell populations. This study shows that depletion of Tregs in human PBMCs infected with Mtb H37Ra in vitro leads to a shift from a Th1 to a Th2 cytokine rich environment that supports the survival of Mtb in this model.
Identifiants
pubmed: 33300047
pii: 5974523
doi: 10.1093/femspd/ftaa068
pii:
doi:
Substances chimiques
BCG Vaccine
0
Cytokines
0
Interleukin-17
0
Interleukin-6
0
Tumor Necrosis Factor-alpha
0
Interleukin-10
130068-27-8
Interleukin-4
207137-56-2
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of FEMS..