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Michael Weber

About Michael Weber:
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SEEK ID: https://funginet.hki-jena.de/people/110

Location:  Germany

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FungiNet total: inactive since 2018-04-01
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Programme: Collaborative Research Center / Transregio 124 "Pathogenic fungi and their human host: Networks of Interaction - FungiNet"

Public web page: http://www.funginet.de/home.html

INF: inactive since 2018-04-01

Integrated database for experimental data

Within the Collaborative Research Center / Transregio 124 “Pathogenic fungi and their human host: Networks of Interaction – FungiNet”, the INF project is responsible to analyse and share OMICS data. Databases help to foster the collaboration within FungiNet as an important point of the Collaborative Research Center. Therefore, we set-up two databases:

a) SEEK is a web-based platform to find, share and exchange unstructured data and knowledge, such as
...

Programme: Collaborative Research Center / Transregio 124 "Pathogenic fungi and their human host: Networks of Interaction - FungiNet"

Public web page: http://www.funginet.de/project-inf.html

Reconstituting NK Cells After Allogeneic Stem Cell Transplantation Show Impaired Response to the Fungal Pathogen Aspergillus fumigatus.
INF, A2, A3, C3

Abstract (Expand)

Delayed natural killer (NK) cell reconstitution after allogeneic stem cell transplantation (alloSCT) is associated with a higher risk of developing invasive aspergillosis. The interaction of NK cells … with the human pathogen Aspergillus (A.) fumigatus is mediated by the fungal recognition receptor CD56, which is relocated to the fungal interface after contact. Blocking of CD56 signaling inhibits the fungal mediated chemokine secretion of MIP-1alpha, MIP-1beta, and RANTES and reduces cell activation, indicating a functional role of CD56 in fungal recognition. We collected peripheral blood from recipients of an allograft at defined time points after alloSCT (day 60, 90, 120, 180). NK cells were isolated, directly challenged with live A. fumigatus germ tubes, and cell function was analyzed and compared to healthy age and gender-matched individuals. After alloSCT, NK cells displayed a higher percentage of CD56(bright)CD16(dim) cells throughout the time of blood collection. However, CD56 binding and relocalization to the fungal contact side were decreased. We were able to correlate this deficiency to the administration of corticosteroid therapy that further negatively influenced the secretion of MIP-1alpha, MIP-1beta, and RANTES. As a consequence, the treatment of healthy NK cells ex vivo with corticosteroids abrogated chemokine secretion measured by multiplex immunoassay. Furthermore, we analyzed NK cells regarding their actin cytoskeleton by Structured Illumination Microscopy (SIM) and flow cytometry and demonstrate an actin dysfunction of NK cells shown by reduced F-actin content after fungal co-cultivation early after alloSCT. This dysfunction remains until 180 days post-alloSCT, concluding that further actin-dependent cellular processes may be negatively influenced after alloSCT. To investigate the molecular pathomechansism, we compared CD56 receptor mobility on the plasma membrane of healthy and alloSCT primary NK cells by single-molecule tracking. The results were very robust and reproducible between tested conditions which point to a different molecular mechanism and emphasize the importance of proper CD56 mobility.

Authors: Esther Weiß, J. Schlegel, Ulrich Terpitz, Michael Weber, Jörg Linde, A. L. Schmitt, Kerstin Hünniger, Lothar Marischen, F. Gamon, J. Bauer, C. Loffler, Oliver Kurzai, C. O. Morton, M. Sauer, Hermann Einsele, Jürgen Löffler

Date Published: 5th Oct 2020

Journal: Front Immunol

Treatment with etanercept and low monocyte concentration contribute to the risk of invasive aspergillosis in patients post allogeneic stem cell transplantation.
INF, A2, C3

Abstract (Expand)

Invasive aspergillosis (IA) is a life-threatening complication among allogeneic hematopoietic stem cell transplant (alloSCT) recipients. Despite well known risk factors and different available assays, … diagnosis of invasive aspergillosis remains challenging. 103 clinical variables from patients with hematological malignancies and subsequent alloSCT were collected. Associations between collected variables and patients with (n = 36) and without IA (n = 36) were investigated by applying univariate and multivariable logistic regression. The predictive power of the final model was tested in an independent patient cohort (23 IA cases and 25 control patients). Findings were investigated further by in vitro studies, which analysed the effect of etanercept on A. fumigatus-stimulated macrophages at the gene expression and cytokine secretion. Additionally, the release of C-X-C motif chemokine ligand 10 (CXCL10) in patient sera was studied. Low monocyte concentration (p = 4.8 x 10(-06)), severe GvHD of the gut (grade 2-4) (p = 1.08 x 10(-02)) and etanercept treatment of GvHD (p = 3.5 x 10(-03)) were significantly associated with IA. Our studies showed that etanercept lowers CXCL10 concentrations in vitro and ex vivo and down-regulates genes involved in immune responses and TNF-alpha signaling. Our study offers clinicians new information regarding risk factors for IA including low monocyte counts and administration of etanercept. After necessary validation, such information may be used for decision making regarding antifungal prophylaxis or closely monitoring patients at risk.

Authors: T. Zoran, Michael Weber, J. Springer, P. L. White, J. Bauer, A. Schober, C. Loffler, B. Seelbinder, Kerstin Hünniger, Oliver Kurzai, A. Scherag, Sascha Schäuble, C. O. Morton, Hermann Einsele, Jörg Linde, Jürgen Löffler

Date Published: 21st Nov 2019

Journal: Sci Rep

Candida albicans Induces Metabolic Reprogramming in Human NK Cells and Responds to Perforin with a Zinc Depletion Response
FungiNet A - Aspergillus projects, FungiNet C - Candida projects

Abstract (Expand)

As part of the innate immune system, natural killer (NK) cells are directly involved in the response to fungal infections. Perforin has been identified as the major effector molecule acting against … many fungal pathogens. While several studies have shown that perforin mediated fungicidal effects can contribute to fungal clearance, neither the activation of NK cells by fungal pathogens nor the effects of perforin on fungal cells are well-understood. In a dual approach, we have studied the global gene expression pattern of primary and cytokine activated NK cells after co-incubation with Candida albicans and the transcriptomic adaptation of C. albicans to perforin exposure. NK cells responded to the fungal pathogen with an up-regulation of genes involved in immune signaling and release of cytokines. Furthermore, we observed a pronounced increase of genes involved in glycolysis and glycolysis inhibitor 2-deoxy-D-glucose impaired C. albicans induced NK cell activation. This strongly indicates that metabolic adaptation is a major part of the NK cell response to C. albicans infections. In the fungal pathogen, perforin induced a strong up-regulation of several fungal genes involved in the zinc depletion response, such as PRA1 and ZRT1. These data suggest that fungal zinc homeostasis is linked to the reaction to perforin secreted by NK cells. However, deletion mutants in PRA1 and ZRT1 did not show altered susceptibility to perforin.

Authors: Dragana Slavkovic Lukic, J. Voigt, M. Bouzani, Jürgen Löffler, Daniela Albrecht-Eckardt, Michael Weber, Stefanie Allert, R. Martin, Oliver Kurzai, Kerstin Hünniger

Date Published: 19th May 2016

Journal: Front Microbiol

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