@article{SilvaVilchesPletinckxLohnertetal.2017,
  author    = {Silva-Vilches, Cinthia and Pletinckx, Katrien and Lohnert, Miriam and Pavlovic, Vladimir and Ashour, Diyaaeldin and John, Vini and Vendelova, Emilia and Kneitz, Susanne and Zhou, Jie and Chen, Rena and Reinheckel, Thomas and Mueller, Thomas D. and Bodem, Jochen and Lutz, Manfred B.},
  title     = {Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {7},
  doi       = {10.1371/journal.pone.0178114},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158244},
  pages     = {e0178114},
  year      = {2017},
  abstract  = {Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3\(^{+}\) induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CT\(^{hi}\), CT\(^{lo}\)) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CT\(^{hi}\) conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CT\(^{lo}\)- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3\(^{+}\) iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CT\(^{lo}\)- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3\(^{+}\) Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae.},
  language  = {en}
}
@article{ZimmermannSubotaBatrametal.2017,
  author    = {Zimmermann, Henriette and Subota, Ines and Batram, Christopher and Kramer, Susanne and Janzen, Christian J. and Jones, Nicola G. and Engstler, Markus},
  title     = {A quorum sensing-independent path to stumpy development in Trypanosoma brucei},
  series = {PLoS Pathogens},
  volume    = {13},
  journal   = {PLoS Pathogens},
  number    = {4},
  doi       = {10.1371/journal.ppat.1006324},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158230},
  pages     = {e1006324},
  year      = {2017},
  abstract  = {For persistent infections of the mammalian host, African trypanosomes limit their population size by quorum sensing of the parasite-excreted stumpy induction factor (SIF), which induces development to the tsetse-infective stumpy stage. We found that besides this cell density-dependent mechanism, there exists a second path to the stumpy stage that is linked to antigenic variation, the main instrument of parasite virulence. The expression of a second variant surface glycoprotein (VSG) leads to transcriptional attenuation of the VSG expression site (ES) and immediate development to tsetse fly infective stumpy parasites. This path is independent of SIF and solely controlled by the transcriptional status of the ES. In pleomorphic trypanosomes varying degrees of ES-attenuation result in phenotypic plasticity. While full ES-attenuation causes irreversible stumpy development, milder attenuation may open a time window for rescuing an unsuccessful antigenic switch, a scenario that so far has not been considered as important for parasite survival.},
  language  = {en}
}
@article{GarciaBetancurGoniMorenoHorgeretal.2017,
  author    = {Garc{\´i}a-Betancur, Juan-Carlos and Go{\~n}i-Moreno, Angel and Horger, Thomas and Schott, Melanie and Sharan, Malvika and Eikmeier, Julian and Wohlmuth, Barbara and Zernecke, Alma and Ohlsen, Knut and Kuttler, Christina and Lopez, Daniel},
  title     = {Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus},
  series = {eLife},
  volume    = {6},
  journal   = {eLife},
  number    = {e28023},
  doi       = {10.7554/eLife.28023},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170346},
  year      = {2017},
  abstract  = {A central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus, which generates the phenotypic bifurcation of the cells into two genetically identical but different cell types during the course of an infection. Whereas one cell type promotes the formation of biofilms that contribute to chronic infections, the second type is planktonic and produces the toxins that contribute to acute bacteremia. We identified a bimodal switch in the agr quorum sensing system that antagonistically regulates the differentiation of these two physiologically distinct cell types. We found that extracellular signals affect the behavior of the agr bimodal switch and modify the size of the specialized subpopulations in specific colonization niches. For instance, magnesium-enriched colonization niches causes magnesium binding to S. aureusteichoic acids and increases bacterial cell wall rigidity. This signal triggers a genetic program that ultimately downregulates the agr bimodal switch. Colonization niches with different magnesium concentrations influence the bimodal system activity, which defines a distinct ratio between these subpopulations; this in turn leads to distinct infection outcomes in vitro and in an in vivo murine infection model. Cell differentiation generates physiological heterogeneity in clonal bacterial infections and helps to determine the distinct infection types.},
  language  = {en}
}