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

Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 1273201 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-4141 (Electronic) Linking ISSN: 00142980 NLM ISO Abbreviation: Eur J Immunol Subsets: MEDLINE

Publication: <2005->: Weinheim : Wiley-VCH
Original Publication: Weinheim, Verlag Chemie GmbH.

Antifungal Agents/*immunology ; Aspergillus/*immunology ; Aspergillus fumigatus/*immunology ; Sus scrofa/*immunology; Animals ; Disease Models, Animal ; Host-Pathogen Interactions/immunology ; Humans ; Lung/immunology ; Spores, Fungal/immunology ; Swine ; Th1 Cells/immunology

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.
(© 2020 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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subproject 03ZZ0813D International German Federal Ministry of Education and Research (BMBF), InfectControl 2020 project ART4Fun; subproject 03ZZ0813C International German Federal Ministry of Education and Research (BMBF), InfectControl 2020 project ART4Fun

Keywords: Aspergillus fumigatus; Fungal aerosolization; Porcine large animal model; Pulmonary immune response; T cells

0 (Antifungal Agents)

Date Created: 20200620 Date Completed: 20210201 Latest Revision: 20210201

20221213

10.1002/eji.201948524

32558930