@article{RibechiniEckertBeilhacketal.2019,
  author    = {Ribechini, Eliana and Eckert, Ina and Beilhack, Andreas and Du Plessis, Nelita and Walzl, Gerhard and Schleicher, Ulrike and Ritter, Uwe and Lutz, Manfred B.},
  title     = {Heat-killed Mycobacterium tuberculosis prime-boost vaccination induces myeloid-derived suppressor cells with spleen dendritic cell-killing capability},
  series = {JCI Insight},
  volume    = {13},
  journal   = {JCI Insight},
  number    = {4},
  doi       = {10.1172/jci.insight.128664},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201973},
  pages     = {e128664},
  year      = {2019},
  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\(^+\) 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.},
  language  = {en}
}
@article{DoehlerSchneiderEckertetal.2017,
  author    = {D{\"o}hler, Anja and Schneider, Theresa and Eckert, Ina and Ribechini, Eliana and Andreas, Nico and Riemann, Marc and Reizis, Boris and Weih, Falk and Lutz, Manfred B.},
  title     = {RelB\(^{+}\) Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the Natural Foxp3\(^{+}\) Regulatory T Cells},
  series = {Frontiers in Immunology},
  volume    = {8},
  journal   = {Frontiers in Immunology},
  number    = {726},
  doi       = {10.3389/fimmu.2017.00726},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158121},
  year      = {2017},
  abstract  = {Thymus-derived natural Foxp3\(^{+}\) CD4\(^{+}\) regulatory T cells (nTregs) play a key role in maintaining immune tolerance and preventing autoimmune disease. Several studies indicate that dendritic cells (DCs) are critically involved in the maintenance and proliferation of nTregs. However, the mechanisms how DCs manage to keep the peripheral pool at constant levels remain poorly understood. Here, we describe that the NF-κB/Rel family transcription factor RelB controls the frequencies of steady-state migratory DCs (ssmDCs) in peripheral lymph nodes and their numbers control peripheral nTreg homeostasis. DC-specific RelB depletion was investigated in CD11c-Cre × RelB\(^{fl/fl}\) mice (RelB\(^{DCko}\)), which showed normal frequencies of resident DCs in lymph nodes and spleen while the subsets of CD103\(^{-}\) Langerin\(^{-}\) dermal DCs (dDCs) and Langerhans cells but not CD103\(^{+}\) Langerin\(^{+}\) dDC of the ssmDCs in skin-draining lymph nodes were increased. Enhanced frequencies and proliferation rates were also observed for nTregs and a small population of CD4\(^{+}\) CD44\(^{high}\) CD25\(^{low}\) memory-like T cells (Tml). Interestingly, only the Tml but not DCs showed an increase in IL-2-producing capacity in lymph nodes of RelB\(^{DCko}\) mice. Blocking of IL-2 in vivo reduced the frequency of nTregs but increased the Tml frequencies, followed by a recovery of nTregs. Taken together, by employing RelB\(^{DCko}\) mice with increased frequencies of ssmDCs our data indicate a critical role for specific ssmDC subsets for the peripheral nTreg and IL-2\(^{+}\) Tml frequencies during homeostasis.},
  language  = {en}
}