Heat-killed Mycobacterium tuberculosis prime-boost vaccination induces myeloid-derived suppressor cells with spleen dendritic cell–killing capability

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dc.contributor.authorRibechini, Elianaen_ZA
dc.contributor.authorEckert, Inaen_ZA
dc.contributor.authorBeilhack, Andreasen_ZA
dc.contributor.authorDu Plessis, Nelitaen_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorSchleicher, Ulrikeen_ZA
dc.contributor.authorRitter, Uween_ZA
dc.contributor.authorLutz, Manfred B.en_ZA
dc.date.accessioned2021-10-19T14:24:00Z
dc.date.available2021-10-19T14:24:00Z
dc.date.issued2019
dc.descriptionCITATION: Ribechini, E., et al. 2019. Heat-killed Mycobacterium tuberculosis prime-boost vaccination induces myeloid-derived suppressor cells with spleen dendritic cell–killing capability. JCI Insight, 4(13):e128664, doi:0.1172/jci.insight.128664.
dc.descriptionThe original publication is available at https://insight.jci.org
dc.description.abstractENGLISH ABSTRACT: Tuberculosis patients and mice infected with live Mycobacterium tuberculosis accumulate high numbers of myeloid-derived suppressor cells (MDSCs). Here, we hypothesized that dead M. tuberculosis vaccines also may induce MDSCs that could impair the efficacy of vaccination. We found that repeated injections of M. tuberculosis vaccines (heat-killed M. tuberculosis in incomplete Freund’s adjuvant, such as Montanide) but not single or control vaccines without M. tuberculosis strongly expanded CD11b+ myeloid cells in the spleen, leading to T cell suppression of proliferation and killing ex vivo. Dead M. tuberculosis vaccination induced the generation of CD11b+Ly6ChiCD115+ iNOS/Nos2+ monocytic MDSCs (M-MDSCs) upon application of inflammatory or microbial activation signals. In vivo these M-MDSCs were positioned strategically in the splenic bridging channels and then positioned in the white pulp areas. Notably, within 6–24 hours, in a Nos2-dependent fashion, they produced NO to rapidly kill conventional and plasmacytoid DCs while, surprisingly, sparing T cells in vivo. Thus, we demonstrate that M. tuberculosis vaccine induced M-MDSCs do not directly suppress effector T cells in vivo but, instead, indirectly by killing DCs. Collectively, we demonstrate that M. tuberculosis booster vaccines induce M-MDSCs in the spleen that can be activated to kill DCs. Our data suggest that formation of MDSCs by M. tuberculosis vaccines should be investigated also in clinical trials.en_ZA
dc.description.urihttps://insight.jci.org/articles/view/128664
dc.description.versionPublisher's version
dc.format.extent17 pagesen_ZA
dc.identifier.citationRibechini, E., et al. 2019. Heat-killed Mycobacterium tuberculosis prime-boost vaccination induces myeloid-derived suppressor cells with spleen dendritic cell–killing capability. JCI Insight, 4(13):e128664, doi:0.1172/jci.insight.128664
dc.identifier.issn2379-3708 (online)
dc.identifier.otherdoi:0.1172/jci.insight.128664
dc.identifier.urihttp://hdl.handle.net/10019.1/123260
dc.language.isoen_ZAen_ZA
dc.publisherAmerican Society for Clinical Investigationen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectTuberculosis patientsen_ZA
dc.subjectMycobacterium tuberculosis -- Vaccinesen_ZA
dc.subjectSpleen -- Diseasesen_ZA
dc.subjectDendritic cellsen_ZA
dc.titleHeat-killed Mycobacterium tuberculosis prime-boost vaccination induces myeloid-derived suppressor cells with spleen dendritic cell–killing capabilityen_ZA
dc.typeArticleen_ZA
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