Human Monocytic Suppressive Cells Promote Replication of Mycobacterium tuberculosis and Alter Stability of in vitro Generated Granulomas

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...

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Bibliographic Details
Published in:Frontiers in immunology 2018-10, Vol.9, p.2417-2417
Main Authors: Agrawal, Neha, Streata, Ioana, Pei, Gang, Weiner, January, Kotze, Leigh, Bandermann, Silke, Lozza, Laura, Walzl, Gerhard, du Plessis, Nelita, Ioana, Mihai, Kaufmann, Stefan H E, Dorhoi, Anca
Format: Article
Language:English
Subjects:
granuloma
IL-10
Immunology
Mycobacterium tuberculosis
myeloid-derived suppressor cells
PD-L1
tuberculosis
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Summary: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 ( ) and their impact on granulomas remain undefined. We generated human monocytic MDSCs and observed that their suppressive capacities are retained upon infection. We employed an 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 generated granulomas. Moreover, MDSCs upregulated PD-L1 and suppressed proliferation of lymphocytes, albeit with negligible effects on 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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2018.02417