Human monocytic suppressive cells promote replication of mycobacterium tuberculosis and alter stability of in vitro generated granulomas

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dc.contributor.authorAgrawal, Nehaen_ZA
dc.contributor.authorStreata, Ioanaen_ZA
dc.contributor.authorPei, Gangen_ZA
dc.contributor.authorWeiner, Januaryen_ZA
dc.contributor.authorKotze, Leighen_ZA
dc.contributor.authorBandermann, Silkeen_ZA
dc.contributor.authorLozza, Lauraen_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorDu Plessis, Nelitaen_ZA
dc.contributor.authorIoana, Mihaien_ZA
dc.contributor.authorKaufmann, Stefan H. E.en_ZA
dc.contributor.authorDorhoi, Ancaen_ZA
dc.date.accessioned2019-09-25T13:07:17Z
dc.date.available2019-09-25T13:07:17Z
dc.date.issued2018
dc.descriptionCITATION: Agrawal, N., et al. 2018. Human monocytic suppressive cells promote replication of mycobacterium tuberculosis and alter stability of in vitro generated granulomas. Frontiers in Immunology, 9:2417, doi:10.3389/fimmu.2018.02417.
dc.descriptionThe original publication is available at https://www.frontiersin.org
dc.description.abstractENGLISH 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.en_ZA
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fimmu.2018.02417/full
dc.description.versionPublisher's version
dc.format.extent19 pagesen_ZA
dc.identifier.citationAgrawal, N., et al. 2018. Human monocytic suppressive cells promote replication of mycobacterium tuberculosis and alter stability of in vitro generated granulomas. Frontiers in Immunology, 9:2417, doi:10.3389/fimmu.2018.02417
dc.identifier.issn1664-3224 (online)
dc.identifier.otherdoi:10.3389/fimmu.2018.02417
dc.identifier.urihttp://hdl.handle.net/10019.1/106522
dc.language.isoen_ZAen_ZA
dc.publisherFrontiers Mediaen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectMycobacterium tuberculosisen_ZA
dc.subjectTuberculosis -- Vaccinationen_ZA
dc.subjectTuberculosis -- Diagnosisen_ZA
dc.titleHuman monocytic suppressive cells promote replication of mycobacterium tuberculosis and alter stability of in vitro generated granulomasen_ZA
dc.typeArticleen_ZA
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