@article{LeonhardtSpielbergWeberetal.2015,
  author    = {Leonhardt, Ines and Spielberg, Steffi and Weber, Michael and Albrecht-Eckardt, Daniela and Bl{\"a}ss, Markus and Claus, Ralf and Barz, Dagmar and Scherlach, Kirstin and Hertweck, Christian and L{\"o}ffler, J{\"u}rgen and H{\"u}nniger, Kerstin and Kurzai, Oliver},
  title     = {The fungal quorum-sensing molecule farnesol activates innate immune cells but suppresses cellular adaptive immunity},
  series = {mBio},
  volume    = {6},
  journal   = {mBio},
  number    = {2},
  doi       = {10.1128/mBio.00143-15},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143756},
  pages     = {e00143-15},
  year      = {2015},
  abstract  = {Farnesol, produced by the polymorphic fungus Candida albicans, is the first quorum-sensing molecule discovered in eukaryotes. Its main function is control of C. albicans filamentation, a process closely linked to pathogenesis. In this study, we analyzed the effects of farnesol on innate immune cells known to be important for fungal clearance and protective immunity. Farnesol enhanced the expression of activation markers on monocytes (CD86 and HLA-DR) and neutrophils (CD66b and CD11b) and promoted oxidative burst and the release of proinflammatory cytokines (tumor necrosis factor alpha [TNF-\(\alpha\)] and macrophage inflammatory protein 1 alpha [MIP-1 \(\alpha\)]). However, this activation did not result in enhanced fungal uptake or killing. Furthermore, the differentiation of monocytes to immature dendritic cells (iDC) was significantly affected by farnesol. Several markers important for maturation and antigen presentation like CD1a, CD83, CD86, and CD80 were significantly reduced in the presence of farnesol. Furthermore, farnesol modulated migrational behavior and cytokine release and impaired the ability of DC to induce T cell proliferation. Of major importance was the absence of interleukin 12 (IL-12) induction in iDC generated in the presence of farnesol. Transcriptome analyses revealed a farnesol-induced shift in effector molecule expression and a down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor during monocytes to iDC differentiation. Taken together, our data unveil the ability of farnesol to act as a virulence factor of C. albicans by influencing innate immune cells to promote inflammation and mitigating the Th1 response, which is essential for fungal clearance.},
  language  = {en}
}
@article{IrmerTarazonaSasseetal.2015,
  author    = {Irmer, Henriette and Tarazona, Sonia and Sasse, Christoph and Olbermann, Patrick and Loeffler, J{\"u}rgen and Krappmann, Sven and Conesa, Ana and Braus, Gerhard H.},
  title     = {RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior},
  series = {BMC Genomics},
  volume    = {16},
  journal   = {BMC Genomics},
  number    = {640},
  doi       = {10.1186/s12864-015-1853-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151390},
  year      = {2015},
  abstract  = {Background: Invasive aspergillosis is started after germination of Aspergillus fumigatus conidia that are inhaled by susceptible individuals. Fungal hyphae can grow in the lung through the epithelial tissue and disseminate hematogenously to invade into other organs. Low fungaemia indicates that fungal elements do not reside in the bloodstream for long. Results: We analyzed whether blood represents a hostile environment to which the physiology of A. fumigatus has to adapt. An in vitro model of A. fumigatus infection was established by incubating mycelium in blood. Our model allowed to discern the changes of the gene expression profile of A. fumigatus at various stages of the infection. The majority of described virulence factors that are connected to pulmonary infections appeared not to be activated during the blood phase. Three active processes were identified that presumably help the fungus to survive the blood environment in an advanced phase of the infection: iron homeostasis, secondary metabolism, and the formation of detoxifying enzymes. Conclusions: We propose that A. fumigatus is hardly able to propagate in blood. After an early stage of sensing the environment, virtually all uptake mechanisms and energy-consuming metabolic pathways are shut-down. The fungus appears to adapt by trans-differentiation into a resting mycelial stage. This might reflect the harsh conditions in blood where A. fumigatus cannot take up sufficient nutrients to establish self-defense mechanisms combined with significant growth.},
  language  = {en}
}
@article{CzakaiLeonhardtDixetal.2016,
  author    = {Czakai, Kristin and Leonhardt, Ines and Dix, Andreas and Bonin, Michael and Linde, Joerg and Einsele, Hermann and Kurzai, Oliver and Loeffler, J{\"u}rgen},
  title     = {Kr{\"u}ppel-like Factor 4 modulates interleukin-6 release in human dendritic cells after in vitro stimulation with Aspergillus fumigatus and Candida albicans},
  series = {Scientific Reports},
  volume    = {6},
  journal   = {Scientific Reports},
  doi       = {10.1038/srep27990},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181185},
  year      = {2016},
  abstract  = {Invasive fungal infections are associated with high mortality rates and are mostly caused by the opportunistic fungi Aspergillus fumigatus and Candida albicans. Immune responses against these fungi are still not fully understood. Dendritic cells (DCs) are crucial players in initiating innate and adaptive immune responses against fungal infections. The immunomodulatory effects of fungi were compared to the bacterial stimulus LPS to determine key players in the immune response to fungal infections. A genome wide study of the gene regulation of human monocyte-derived dendritic cells (DCs) confronted with A. fumigatus, C. albicans or LPS was performed and Kr{\"u}ppel-like factor 4 (KLF4) was identified as the only transcription factor that was down-regulated in DCs by both fungi but induced by stimulation with LPS. Downstream analysis demonstrated the influence of KLF4 on the interleukine-6 expression in human DCs. Furthermore, KLF4 regulation was shown to be dependent on pattern recognition receptor ligation. Therefore KLF4 was identified as a controlling element in the IL-6 immune response with a unique expression pattern comparing fungal and LPS stimulation.},
  language  = {en}
}