TY  - JOUR
A1  - Ruf, Dominik
A1  - Brantl, Victor
A1  - Wagener, Johannes
T1  - Mitochondrial Fragmentation in \(Aspergillus\) \(fumigatus\) as Early Marker of Granulocyte Killing Activity
JF  - Frontiers in Cellular and Infection Microbiology
N2  - The host's defense against invasive mold infections relies on diverse antimicrobial activities of innate immune cells. However, studying these mechanisms in vitro is complicated by the filamentous nature of such pathogens that typically form long, branched, multinucleated and compartmentalized hyphae. Here we describe a novel method that allows for the visualization and quantification of the antifungal killing activity exerted by human granulocytes against hyphae of the opportunistic pathogen Aspergillus fumigatus. The approach relies on the distinct impact of fungal cell death on the morphology of mitochondria that were visualized with green fluorescent protein (GFP). We show that oxidative stress induces complete fragmentation of the tubular mitochondrial network which correlates with cell death of affected hyphae. Live cell microscopy revealed a similar and non-reversible disruption of the mitochondrial morphology followed by fading of fluorescence in Aspergillus hyphae that were killed by human granulocytes. Quantitative microscopic analysis of fixed samples was subsequently used to estimate the antifungal activity. By utilizing this assay, we demonstrate that lipopolysaccharides as well as human serum significantly increase the killing efficacy of the granulocytes. Our results demonstrate that evaluation of the mitochondrial morphology can be utilized to assess the fungicidal activity of granulocytes against A. fumigatus hyphae.
KW  - Aspergillus fumigatus
KW  - killing
KW  - assay
KW  - PMNs
KW  - granulocytes
KW  - mitochondria
KW  - mitochondrial morphology
KW  - fungicidal activity
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227133
VL  - 8
IS  - 128
ER  - 
TY  - JOUR
A1  - Reimann, Hauke
A1  - Stopper, Helga
A1  - Polak, Thomas
A1  - Lauer, Martin
A1  - Herrmann, Martin J.
A1  - Deckert, Jürgen
A1  - Hintzsche, Henning
T1  - Micronucleus frequency in buccal mucosa cells of patients with neurodegenerative diseases
JF  - Scientific Reports
N2  - Neurodegenerative diseases show an increase in prevalence and incidence, with the most prominent example being Alzheimer's disease. DNA damage has been suggested to play a role in the pathogenesis, but the exact mechanisms remain elusive. We enrolled 425 participants with and without neurodegenerative diseases and analyzed DNA damage in the form of micronuclei in buccal mucosa samples. In addition, other parameters such as binucleated cells, karyolytic cells, and karyorrhectic cells were quantified. No relevant differences in DNA damage and cytotoxicity markers were observed in patients compared to healthy participants. Furthermore, other parameters such as lifestyle factors and diseases were also investigated. Overall, this study could not identify a direct link between changes in buccal cells and neurogenerative diseases, but highlights the influence of lifestyle factors and diseases on the human buccal cytome.
KW  - peripheral-blood lymphocytes
KW  - Alzheimers disease
KW  - DNA damage
KW  - cognitive impairment
KW  - cytome biomarkers
KW  - diagnosis
KW  - association
KW  - assay
KW  - life
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231430
VL  - 10
ER  -