TY - JOUR A1 - Belic, Stanislav A1 - Page, Lukas A1 - Lazariotou, Maria A1 - Waaga-Gasser, Ana Maria A1 - Dragan, Mariola A1 - Springer, Jan A1 - Loeffler, Juergen A1 - Morton, Charles Oliver A1 - Einsele, Hermann A1 - Ullmann, Andrew J. A1 - Wurster, Sebastian T1 - Comparative Analysis of Inflammatory Cytokine Release and Alveolar Epithelial Barrier Invasion in a Transwell® Bilayer Model of Mucormycosis JF - Frontiers in Microbiology N2 - Understanding the mechanisms of early invasion and epithelial defense in opportunistic mold infections is crucial for the evaluation of diagnostic biomarkers and novel treatment strategies. Recent studies revealed unique characteristics of the immunopathology of mucormycoses. We therefore adapted an alveolar Transwell® A549/HPAEC bilayer model for the assessment of epithelial barrier integrity and cytokine response to Rhizopus arrhizus, Rhizomucor pusillus, and Cunninghamella bertholletiae. Hyphal penetration of the alveolar barrier was validated by 18S ribosomal DNA detection in the endothelial compartment. Addition of dendritic cells (moDCs) to the alveolar compartment led to reduced fungal invasion and strongly enhanced pro-inflammatory cytokine response, whereas epithelial CCL2 and CCL5 release was reduced. Despite their phenotypic heterogeneity, the studied Mucorales species elicited the release of similar cytokine patterns by epithelial and dendritic cells. There were significantly elevated lactate dehydrogenase concentrations in the alveolar compartment and epithelial barrier permeability for dextran blue of different molecular weights in Mucorales-infected samples compared to Aspergillus fumigatus infection. Addition of monocyte-derived dendritic cells further aggravated LDH release and epithelial barrier permeability, highlighting the influence of the inflammatory response in mucormycosis-associated tissue damage. An important focus of this study was the evaluation of the reproducibility of readout parameters in independent experimental runs. Our results revealed consistently low coefficients of variation for cytokine concentrations and transcriptional levels of cytokine genes and cell integrity markers. As additional means of model validation, we confirmed that our bilayer model captures key principles of Mucorales biology such as accelerated growth in a hyperglycemic or ketoacidotic environment or reduced epithelial barrier invasion upon epithelial growth factor receptor blockade by gefitinib. Our findings indicate that the Transwell® bilayer model provides a reliable and reproducible tool for assessing host response in mucormycosis. KW - mucormycosis KW - alveolar epithelium KW - in vitro model KW - cytokines KW - dendritic cells Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252477 VL - 9 ER - TY - JOUR A1 - Ullmann, Andrew J. A1 - Schmidt-Hieber, Martin A1 - Bertz, Hartmut A1 - Heinz, Werner J. A1 - Kiehl, Michael A1 - Krüger, William A1 - Mousset, Sabine A1 - Neuburger, Stefan A1 - Neumann, Silke A1 - Penack, Olaf A1 - Silling, Gerda A1 - Vehreschild, Jörg Janne A1 - Einsele, Hermann A1 - Maschmeyer, Georg T1 - Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016 JF - Annals of Hematology N2 - Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial agents but includes recommendations on the use of vaccinations. This is the updated version of the AGHIO guideline in the field of allogeneic haematopoietic stem cell transplantation utilizing methods according to evidence-based medicine criteria. KW - Bone-marrow-transplantation KW - Pneumocystis-carinii-pneumonia KW - Influenzae type B KW - Respiratory syncytial virus KW - Infections KW - invasive fungal infections KW - Varicella-Zoster-Virus KW - Hepatitis B virus KW - Herpes simplex virus KW - Human immunodefiency virus KW - Low-dose acyclovir KW - Viral KW - Fungal KW - Bacteria Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187587 VL - 95 IS - 9 ER - TY - JOUR A1 - Mousset, Sabine A1 - Buchheidt, Dieter A1 - Heinz, Werner A1 - Ruhnke, Markus A1 - Cornely, Oliver A. A1 - Egerer, Gerlinde A1 - Krüger, William A1 - Link, Hartmut A1 - Neumann, Silke A1 - Ostermann, Helmut A1 - Panse, Jens A1 - Penack, Olaf A1 - Rieger, Christina A1 - Schmidt-Hieber, Martin A1 - Silling, Gerda A1 - Südhoff, Thomas A1 - Ullmann, Andrew J. A1 - Wolf, Hans-Heinrich A1 - Maschmeyer, Georg A1 - Böhme, Angelika T1 - Treatment of invasive fungal infections in cancer patients—updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) JF - Annals of Hematology N2 - Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. Early antifungal treatment is mandatory to improve survival. Today, a number of effective and better-tolerated but more expensive antifungal agents compared to the former gold standard amphotericin B deoxycholate are available. Clinical decision-making must consider results from numerous studies and published guidelines, as well as licensing status and cost pressure. New developments in antifungal prophylaxis improving survival rates result in a continuous need for actualization. The treatment options for invasive Candida infections include fluconazole, voriconazole, and amphotericin B and its lipid formulations, as well as echinocandins. Voriconazole, amphotericin B, amphotericin B lipid formulations, caspofungin, itraconazole, and posaconazole are available for the treatment of invasive aspergillosis. Additional procedures, such as surgical interventions, immunoregulatory therapy, and granulocyte transfusions, have to be considered. The Infectious Diseases Working Party of the German Society of Hematology and Oncology here presents its 2008 recommendations discussing the dos and do-nots, as well as the problems and possible solutions, of evidence criteria selection. KW - cancer KW - invasive fungal infections KW - antifungals KW - mycoses KW - hematologic malignancies KW - aspergillosis KW - antifungal agents KW - invasive candidiasis Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121340 VL - 96 ER -