TY  - JOUR
A1  - Morton, Charles Oliver
A1  - Fliesser, Mirjam
A1  - Dittrich, Marcus
A1  - Müller, Tobias
A1  - Bauer, Ruth
A1  - Kneitz, Susanne
A1  - Hope, William
A1  - Rogers, Thomas Richard
A1  - Einsele, Hermann
A1  - Löffler, Jürgen
T1  - Gene Expression Profiles of Human Dendritic Cells Interacting with Aspergillus fumigatus in a Bilayer Model of the Alveolar Epithelium/Endothelium Interface
N2  - 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.
KW  - aspergillus fumigatus
KW  - gene expression
KW  - immune receptors
KW  - immune response
KW  - denritic cells
KW  - B cell receptors
KW  - gene regulation
KW  - RNA extraction
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112893
ER  - 
TY  - JOUR
A1  - Wong, David
A1  - Winter, Oliver
A1  - Hartig, Christina
A1  - Siebels, Svenja
A1  - Szyska, Martin
A1  - Tiburzy, Benjamin
A1  - Meng, Lingzhang
A1  - Kulkarni, Upasana
A1  - Fähnrich, Anke
A1  - Bommert, Kurt
A1  - Bargou, Ralf
A1  - Berek, Claudia
A1  - Van, Trung Chu
A1  - Bogen, Bjarne
A1  - Jundt, Franziska
A1  - Manz, Rudolf Armin
T1  - Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches
JF  - PLOS ONE
N2  - Multiple myeloma is a bone marrow plasma cell tumor which is supported by the external growth factors APRIL and IL-6, among others. Recently, we identified eosinophils and megakaryocytes to be functional components of the micro-environmental niches of benign bone marrow plasma cells and to be important local sources of these cytokines. Here, we investigated whether eosinophils and megakaryocytes also support the growth of tumor plasma cells in the MOPC315. BM model for multiple myeloma. As it was shown for benign plasma cells and multiple myeloma cells, IL-6 and APRIL also supported MOPC315. BM cell growth in vitro, IL-5 had no effect. Depletion of eosinophils in vivo by IL-5 blockade led to a reduction of the early myeloma load. Consistent with this, myeloma growth in early stages was retarded in eosinophil-deficient Delta dblGATA-1 mice. Late myeloma stages were unaffected, possibly due to megakaryocytes compensating for the loss of eosinophils, since megakaryocytes were found to be in contact with myeloma cells in vivo and supported myeloma growth in vitro. We conclude that eosinophils and megakaryocytes in the niches for benign bone marrow plasma cells support the growth of malignant plasma cells. Further investigations are required to test whether perturbation of these niches represents a potential strategy for the treatment of multiple myeloma.
KW  - plasma cells
KW  - human multiple-myeloma
KW  - immune response
KW  - receptor expression
KW  - B-cells
KW  - stromal cells
KW  - dexamethasone
KW  - april
KW  - survival
KW  - Interleukin-5
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115269
VL  - 9
IS  - 10
ER  -