@article{MortonFliesserDittrichetal.2014,
  author    = {Morton, Charles Oliver and Fliesser, Mirjam and Dittrich, Marcus and M{\"u}ller, Tobias and Bauer, Ruth and Kneitz, Susanne and Hope, William and Rogers, Thomas Richard and Einsele, Hermann and L{\"o}ffler, J{\"u}rgen},
  title     = {Gene Expression Profiles of Human Dendritic Cells Interacting with Aspergillus fumigatus in a Bilayer Model of the Alveolar Epithelium/Endothelium Interface},
  doi       = {10.1371/journal.pone.0098279},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112893},
  year      = {2014},
  abstract  = {The initial stages of the interaction between the host and Aspergillus fumigatus at the alveolar surface of the human lung are critical in the establishment of aspergillosis. Using an in vitro bilayer model of the alveolus, including both the epithelium (human lung adenocarcinoma epithelial cell line, A549) and endothelium (human pulmonary artery epithelial cells, HPAEC) on transwell membranes, it was possible to closely replicate the in vivo conditions. Two distinct sub-groups of dendritic cells (DC), monocyte-derived DC (moDC) and myeloid DC (mDC), were included in the model to examine immune responses to fungal infection at the alveolar surface. RNA in high quantity and quality was extracted from the cell layers on the transwell membrane to allow gene expression analysis using tailored custom-made microarrays, containing probes for 117 immune-relevant genes. This microarray data indicated minimal induction of immune gene expression in A549 alveolar epithelial cells in response to germ tubes of A. fumigatus. In contrast, the addition of DC to the system greatly increased the number of differentially expressed immune genes. moDC exhibited increased expression of genes including CLEC7A, CD209 and CCL18 in the absence of A. fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups exhibited up-regulation of genes identified in previous studies as being associated with the exposure of DC to A. fumigatus and exhibiting chemotactic properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model closely approximated the human alveolus allowing for an analysis of the host pathogen interface that complements existing animal models of IA.},
  language  = {en}
}
@article{DixCzakaiSpringeretal.2016,
  author    = {Dix, Andreas and Czakai, Kristin and Springer, Jan and Fliesser, Mirjam and Bonin, Michael and Guthke, Reinhard and Schmitt, Anna L. and Einsele, Hermann and Linde, J{\"o}rg and L{\"o}ffler, J{\"u}rgen},
  title     = {Genome-Wide Expression Profiling Reveals S100B as Biomarker for Invasive Aspergillosis},
  series = {Frontiers in Microbiology},
  journal   = {Frontiers in Microbiology},
  number    = {7},
  doi       = {10.3389/fmicb.2016.00320},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165386},
  pages     = {320},
  year      = {2016},
  abstract  = {Invasive aspergillosis (IA) is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk for IA, which is mainly caused by the species Aspergillus fumigatus. An early and reliable diagnosis is required to initiate the appropriate antifungal therapy. However, diagnostic sensitivity and accuracy still needs to be improved, which can be achieved at least partly by the definition of new biomarkers. Besides the direct detection of the pathogen by the current diagnostic methods, the analysis of the host response is a promising strategy toward this aim. Following this approach, we sought to identify new biomarkers for IA. For this purpose, we analyzed gene expression profiles of hematological patients and compared profiles of patients suffering from IA with non-IA patients. Based on microarray data, we applied a comprehensive feature selection using a random forest classifier. We identified the transcript coding for the S100 calcium-binding protein B (S100B) as a potential new biomarker for the diagnosis of IA. Considering the expression of this gene, we were able to classify samples from patients with IA with 82.3\% sensitivity and 74.6\% specificity. Moreover, we validated the expression of S100B in a real-time reverse transcription polymerase chain reaction (RT-PCR) assay and we also found a down-regulation of S100B in A. fumigatus stimulated DCs. An influence on the IL1B and CXCL1 downstream levels was demonstrated by this S100B knockdown. In conclusion, this study covers an effective feature selection revealing a key regulator of the human immune response during IA. S100B may represent an additional diagnostic marker that in combination with the established techniques may improve the accuracy of IA diagnosis.},
  language  = {en}
}