The domestic pig as human-relevant large animal model to study adaptive anti-fungal immune responses against airborne Aspergillus fumigatus.


Stefanie Schmidt, Friederike Ebner, Kerstin Rosen, Olaf Kniemeyer, Axel A Brakhage, Jürgen Löffler, Michelle Seif, Jan Springer, Josephine Schlosser, Lydia Scharek-Tedin, Alexander Scheffold, Petra Bacher, Anja A Kühl, Uwe Rösler, Susanne Hartmann

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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 106 cfu/m3 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 anti-fungal T cell responses more than two 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. This article is protected by copyright. All rights reserved.