Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis.
Adult
Cells, Cultured
Cytokines
/ metabolism
Drug Repositioning
Female
Humans
Immunosuppressive Agents
/ pharmacology
Lymphocyte Activation
Male
Middle Aged
Mycobacterium tuberculosis
/ physiology
Myeloid-Derived Suppressor Cells
/ immunology
T-Lymphocytes
/ drug effects
Tretinoin
/ pharmacology
Tuberculosis, Pulmonary
/ immunology
All-trans retinoic acid
Host-directed therapies
Mycobacterium tuberculosis
Myeloid-derived suppressor cells
Tuberculosis
Journal
Cellular immunology
ISSN: 1090-2163
Titre abrégé: Cell Immunol
Pays: Netherlands
ID NLM: 1246405
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
30
10
2020
revised:
21
03
2021
accepted:
02
04
2021
pubmed:
18
4
2021
medline:
24
11
2021
entrez:
17
4
2021
Statut:
ppublish
Résumé
Conventional anti-tuberculosis (TB) therapies comprise lengthy antibiotic treatment regimens, exacerbated by multi-drug resistant and extensively drug resistant mycobacterial strains. We assessed the ability of all-trans retinoic acid (ATRA), as repurposed compound serving as host-directed therapy (HDT), to counteract the suppressive effects of myeloid-derived suppressor cells (MDSCs) obtained from active TB cases (untreated or during week one of treatment) on T-cell responsiveness. We show for the first time that MDSCs suppress non-specific T-cell activation and production of interleukin (IL)-2, IL-4, IL-13 and GM-CSF via contact-dependent mechanisms. ATRA treatment decreases MDSC frequency, but fails to mature MDSCs to non-suppressive, terminally differentiated myeloid cells and does not restore T-cell function or cytokine production in the presence of MDSCs. The impact of ATRA treatment on improved immunity, using the concentration tested here, is likely to be minimal, but further identification and development of MDSC-targeting TB host-directed therapies are warranted.
Identifiants
pubmed: 33865151
pii: S0008-8749(21)00078-2
doi: 10.1016/j.cellimm.2021.104359
pmc: PMC8493473
mid: NIHMS1693738
pii:
doi:
Substances chimiques
Cytokines
0
Immunosuppressive Agents
0
Tretinoin
5688UTC01R
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104359Subventions
Organisme : NIAID NIH HHS
ID : U01 AI115619
Pays : United States
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
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