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The domestic pig as human-relevant large animal model to study adaptive antifungal immune responses against airborne Aspergillus fumigatus.
European Journal of Immunology ( IF 5.4 ) Pub Date : 2020-06-19 , DOI: 10.1002/eji.201948524
Stefanie Schmidt 1 , Friederike Ebner 1 , Kerstin Rosen 2 , Olaf Kniemeyer 3 , Axel A Brakhage 3 , Jürgen Löffler 4 , Michelle Seif 4 , Jan Springer 4 , Josephine Schlosser 1 , Lydia Scharek-Tedin 1 , Alexander Scheffold 5 , Petra Bacher 5, 6 , Anja A Kühl 7, 8 , Uwe Rösler 2 , Susanne Hartmann 1
Affiliation  

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 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.

中文翻译:

家猪作为与人类有关的大型动物模型,研究针对机载烟曲霉的适应性抗真菌免疫反应。

肺粘膜免疫反应对于预防机会性烟曲霉感染至关重要。尽管描述了血液中的真菌特异性CD4 + T细胞反映了实际的宿主与病原体相互作用的状态,但对曲霉菌特异性的肺T细胞反应知之甚少。在这里,我们利用家猪作为人类相关的大型动物模型,并在猪中引入抗原特异性T细胞富集,以解决与外周血相比肺中曲霉特异性T细胞的问题。在健康,环境暴露于曲霉的猪中,可以在血液中检测到真菌特异性T细胞,其频率与健康人中观察到的频率相似,并表现出Th1表型。暴露于10只猪6 cfu / m 3分生孢子在肺部和全身均诱导曲霉特异性Th1细胞长期积累。曲霉菌暴露期间的临时免疫抑制显示,取消抑制治疗后超过2周,肺部浸润性抗真菌T细胞反应显着降低。这反映在血液中,但程度要小得多。总之,通过使用与人类有关的大型动物模型,该研究强调了血液清楚地反映了环境暴露和实验暴露的健康猪的粘膜真菌特异性T细胞反应性。但是,与最初的全身免疫反应相比,免疫抑制会显着影响粘膜部位。
更新日期:2020-06-19
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