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Human Monocytic Suppressive Cells Promote Replication of Mycobacterium tuberculosis and Alter Stability of in vitro Generated Granulomas.
- Source :
-
Frontiers in immunology [Front Immunol] 2018 Oct 23; Vol. 9, pp. 2417. Date of Electronic Publication: 2018 Oct 23 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- Tuberculosis (TB) has tremendous public health relevance. It most frequently affects the lung and is characterized by the development of unique tissue lesions, termed granulomas. These lesions encompass various immune populations, with macrophages being most extensively investigated. Myeloid derived suppressor cells (MDSCs) have been recently identified in TB patients, both in the circulation and at the site of infection, however their interactions with Mycobacterium tuberculosis ( Mtb ) and their impact on granulomas remain undefined. We generated human monocytic MDSCs and observed that their suppressive capacities are retained upon Mtb infection. We employed an in vitro granuloma model, which mimics human TB lesions to some extent, with the aim of analyzing the roles of MDSCs within granulomas. MDSCs altered the structure of and affected bacterial containment within granuloma-like structures. These effects were partly controlled through highly abundant secreted IL-10. Compared to macrophages, MDSCs activated primarily the NF-κB and MAPK pathways and the latter largely contributed to the release of IL-10 and replication of bacteria within in vitro generated granulomas. Moreover, MDSCs upregulated PD-L1 and suppressed proliferation of lymphocytes, albeit with negligible effects on Mtb replication. Further comprehensive characterization of MDSCs in TB will contribute to a better understanding of disease pathogenesis and facilitate the design of novel immune-based interventions for this deadly infection.
- Subjects :
- B7-H1 Antigen metabolism
Bacterial Load
Cell Proliferation
Cells, Cultured
DNA Replication
Extracellular Signal-Regulated MAP Kinases metabolism
Granuloma, Respiratory Tract microbiology
Humans
Immune Tolerance
Interleukin-10 metabolism
NF-kappa B metabolism
Signal Transduction
Up-Regulation
Granuloma, Respiratory Tract pathology
Lymphocytes immunology
Mycobacterium tuberculosis physiology
Myeloid-Derived Suppressor Cells immunology
Tuberculosis, Pulmonary immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 30405617
- Full Text :
- https://doi.org/10.3389/fimmu.2018.02417