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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Ribechini E, Eckert I, Beilhack A, Du Plessis N, Walzl G, Schleicher U, Ritter U, Lutz MB
Zeitschrift: JCI Insight
Jahr der Veröffentlichung: 2019
Band: 4
Heftnummer: 13
ISSN: 2379-3708


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(+)Ly6C(hi)CD115(+) iNDS/Nos2(+) monocytic MDSCs (M-MDSCs) upon application of inflammatory or microbial activation signals. In vivo these M-M DSCs 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 ND 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.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Schleicher, Ulrike PD Dr.
Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene


Einrichtungen weiterer Autorinnen und Autoren

Julius-Maximilians-Universität Würzburg
Universität Regensburg
Universitätsklinikum Würzburg
University of Stellenbosch / Universiteit van Stellenbosch


Zitierweisen

APA:
Ribechini, E., Eckert, I., Beilhack, A., Du Plessis, N., Walzl, G., Schleicher, U.,... Lutz, M.B. (2019). Heat-killed Mycobacterium tuberculosis prime-boost vaccination induces myeloid-derived suppressor cells with spleen dendritic cell killing capability. JCI Insight, 4(13). https://dx.doi.org/10.1172/jci.insight.128664

MLA:
Ribechini, Eliana, et al. "Heat-killed Mycobacterium tuberculosis prime-boost vaccination induces myeloid-derived suppressor cells with spleen dendritic cell killing capability." JCI Insight 4.13 (2019).

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Zuletzt aktualisiert 2019-26-07 um 21:08