TY  - JOUR
A1  - Schmidt, Stefanie
A1  - Ebner, Friederike
A1  - Rosen, Kerstin
A1  - Kniemeyer, Olaf
A1  - Brakhage, Axel A.
A1  - Löffler, Jürgen
A1  - Seif, Michelle
A1  - Springer, Jan
A1  - Schlosser, Josephine
A1  - Scharek‐Tedin, Lydia
A1  - Scheffold, Alexander
A1  - Bacher, Petra
A1  - Kühl, Anja A.
A1  - Rösler, Uwe
A1  - Hartmann, Susanne
T1  - The domestic pig as human‐relevant large animal model to study adaptive antifungal immune responses against airborne Aspergillus fumigatus
JF  - European Journal of Immunology
N2  - Pulmonary mucosal immune response is critical for preventing opportunistic Aspergillus fumigatus infections. Although fungus‐specific CD4\(^{+}\) T cells in blood are described to reflect the actual host–pathogen interaction status, little is known about Aspergillus‐specific pulmonary T‐cell responses. Here, we exploit the domestic pig as human‐relevant large animal model and introduce antigen‐specific T‐cell enrichment in pigs to address Aspergillus‐specific T cells in the lung compared to peripheral blood. In healthy, environmentally Aspergillus‐exposed pigs, the fungus‐specific T cells are detectable in blood in similar frequencies as observed in healthy humans and exhibit a Th1 phenotype. Exposing pigs to 10\(^{6}\) cfu/m\(^{3}\) conidia induces a long‐lasting accumulation of Aspergillus‐specific Th1 cells locally in the lung and also systemically. Temporary immunosuppression during Aspergillus‐exposure showed a drastic reduction in the lung‐infiltrating antifungal T‐cell responses more than 2 weeks after abrogation of the suppressive treatment. This was reflected in blood, but to a much lesser extent. In conclusion, by using the human‐relevant large animal model the pig, this study highlights that the blood clearly reflects the mucosal fungal‐specific T‐cell reactivity in environmentally exposed as well as experimentally exposed healthy pigs. But, immunosuppression significantly impacts the mucosal site in contrast to the initial systemic immune response.
KW  - fungal aerosolization
KW  - porcine large animal model
KW  - pulmonary immune response
KW  - T cells
KW  - Aspergillus fumigatus
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216085
VL  - 50
IS  - 11
SP  - 1712
EP  - 1728
ER  - 
TY  - JOUR
A1  - Gupta, Shishir K.
A1  - Srivastava, Mugdha
A1  - Osmanoglu, Özge
A1  - Xu, Zhuofei
A1  - Brakhage, Axel A.
A1  - Dandekar, Thomas
T1  - Aspergillus fumigatus versus genus Aspergillus: conservation, adaptive evolution and specific virulence genes
JF  - Microorganisms
N2  - Aspergillus is an important fungal genus containing economically important species, as well as pathogenic species of animals and plants. Using eighteen fungal species of the genus Aspergillus, we conducted a comprehensive investigation of conserved genes and their evolution. This also allows us to investigate the selection pressure driving the adaptive evolution in the pathogenic species A. fumigatus. Among single-copy orthologs (SCOs) for A. fumigatus and the closely related species A. fischeri, we identified 122 versus 50 positively selected genes (PSGs), respectively. Moreover, twenty conserved genes of unknown function were established to be positively selected and thus important for adaption. A. fumigatus PSGs interacting with human host proteins show over-representation of adaptive, symbiosis-related, immunomodulatory and virulence-related pathways, such as the TGF-β pathway, insulin receptor signaling, IL1 pathway and interfering with phagosomal GTPase signaling. Additionally, among the virulence factor coding genes, secretory and membrane protein-coding genes in multi-copy gene families, 212 genes underwent positive selection and also suggest increased adaptation, such as fungal immune evasion mechanisms (aspf2), siderophore biosynthesis (sidD), fumarylalanine production (sidE), stress tolerance (atfA) and thermotolerance (sodA). These genes presumably contribute to host adaptation strategies. Genes for the biosynthesis of gliotoxin are shared among all the close relatives of A. fumigatus as an ancient defense mechanism. Positive selection plays a crucial role in the adaptive evolution of A. fumigatus. The genome-wide profile of PSGs provides valuable targets for further research on the mechanisms of immune evasion, antimycotic targeting and understanding fundamental virulence processes.
KW  - molecular evolution
KW  - phylogenetic analysis
KW  - adaptation
KW  - recombination
KW  - positive selection
KW  - human pathogenic fungi
KW  - genus Aspergillus
KW  - Aspergillus fumigatus
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246318
SN  - 2076-2607
VL  - 9
IS  - 10
ER  -