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  - Tappe, Beeke
A1  - Lauruschkat, Chris D.
A1  - Strobel, Lea
A1  - Pantaleón García, Jezreel
A1  - Kurzai, Oliver
A1  - Rebhan, Silke
A1  - Kraus, Sabrina
A1  - Pfeuffer-Jovic, Elena
A1  - Bussemer, Lydia
A1  - Possler, Lotte
A1  - Held, Matthias
A1  - Hünniger, Kerstin
A1  - Kniemeyer, Olaf
A1  - Schäuble, Sascha
A1  - Brakhage, Axel A.
A1  - Panagiotou, Gianni
A1  - White, P. Lewis
A1  - Einsele, Hermann
A1  - Löffler, Jürgen
A1  - Wurster, Sebastian
T1  - COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
JF  - Frontiers in Immunology
N2  - Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus- and R. arrhizus-induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, whole blood from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients.
KW  - COVID-19
KW  - immune impairment
KW  - T cells
KW  - granulocytes
KW  - Aspergillus
KW  - Rhizopus
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283558
SN  - 1664-3224
VL  - 13
ER  -