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  - Seif, Michelle
A1  - Einsele, Hermann
A1  - Löffler, Jürgen
T1  - CAR T cells beyond cancer: hope for immunomodulatory therapy of infectious diseases
JF  - Frontiers in Immunology
N2  - Infectious diseases are still a significant cause of morbidity and mortality worldwide. Despite the progress in drug development, the occurrence of microbial resistance is still a significant concern. Alternative therapeutic strategies are required for non-responding or relapsing patients. Chimeric antigen receptor (CAR) T cells has revolutionized cancer immunotherapy, providing a potential therapeutic option for patients who are unresponsive to standard treatments. Recently two CAR T cell therapies, Yescarta® (Kite Pharma/Gilead) and Kymriah® (Novartis) were approved by the FDA for the treatments of certain types of non-Hodgkin lymphoma and B-cell precursor acute lymphoblastic leukemia, respectively. The success of adoptive CAR T cell therapy for cancer has inspired researchers to develop CARs for the treatment of infectious diseases. Here, we review the main achievements in CAR T cell therapy targeting viral infections, including Human Immunodeficiency Virus, Hepatitis C Virus, Hepatitis B Virus, Human Cytomegalovirus, and opportunistic fungal infections such as invasive aspergillosis.
KW  - infectious diseases
KW  - mAb engineering
KW  - CAR T cells
KW  - HIV
KW  - HCV
KW  - CMV
KW  - invasive aspergillosis
KW  - HBV
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195596
SN  - 1664-3224
VL  - 10
IS  - 2711
ER  - 
TY  - JOUR
A1  - White, P. Lewis
A1  - Springer, Jan
A1  - Wise, Matt P.
A1  - Einsele, Hermann
A1  - Löffler, Claudia
A1  - Seif, Michelle
A1  - Prommersberger, Sabrina
A1  - Backx, Matthijs
A1  - Löffler, Jürgen
T1  - A clinical case of COVID-19-associated pulmonary aspergillosis (CAPA), illustrating the challenges in diagnosis (despite overwhelming mycological evidence)
JF  - Journal of Fungi
N2  - The COVID-19 pandemic has resulted in large numbers of patients requiring critical care management. With the established association between severe respiratory virus infection and invasive pulmonary aspergillosis (7.6% for COVID-19-associated pulmonary aspergillosis (CAPA)), the pandemic places a significant number of patients at potential risk from secondary invasive fungal disease. We described a case of CAPA with substantial supporting mycological evidence, highlighting the need to employ strategic diagnostic algorithms and weighted definitions to improve the accuracy in diagnosing CAPA.
KW  - COVID-19
KW  - CAPA
KW  - diagnostics
KW  - Aspergillus
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-302438
SN  - 2309-608X
VL  - 8
IS  - 1
ER  -