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屏障饲养和性别对鼠屋尘螨模型变应性气道疾病的影响。

Barrier Housing and Gender Effects on Allergic Airway Disease in a Murine House Dust Mite Model.

机构信息

Department of Inflammation and Immunity, Lerner Research Institute, Cleveland, OH 44195.

Center for Microbiome and Human Health, Lerner Research Institute, Cleveland, OH 44195.

出版信息

Immunohorizons. 2021 Jan 21;5(1):33-47. doi: 10.4049/immunohorizons.2000096.

Abstract

Allergic airway disease models use laboratory mice housed in highly controlled and hygienic environments, which provide a barrier between the mice and a predetermined list of specific pathogens excluded from the facility. In this study, we hypothesized that differences in facility barrier level and, consequently, the hygienic quality of the environment that mice inhabit impact the severity of pulmonary inflammation and lung function. Allergen-naive animals housed in the cleaner, high barrier (HB) specific pathogen-free facility had increased levels of inflammatory cytokines and higher infiltration of immune cells in the lung tissue but not in the bronchoalveolar lavage compared with mice housed in the less hygienic, low barrier specific pathogen-free facility. In both genders, house dust mite-induced airway disease was more severe in the HB than the low barrier facility. Within each barrier facility, female mice developed the most severe inflammation. However, allergen-naive male mice had worse lung function, regardless of the housing environment, and in the HB, the lung function in female mice was higher in the house dust mite model. Severe disease in the HB was associated with reduced lung microbiome diversity. The lung microbiome was altered across housing barriers, gender, and allergen-exposed groups. Thus, the housing barrier level impacts microbial-driven disease and gender phenotypes in allergic asthma. The housing of laboratory mice in more clean HB facilities aggravates lung immunity and causes a more severe allergic lung disease.

摘要

变应性气道疾病模型使用饲养在高度控制和卫生环境中的实验小鼠,这些环境为小鼠和设施中排除的预定特定病原体之间提供了一道屏障。在这项研究中,我们假设设施屏障水平的差异,以及因此小鼠所居住的环境的卫生质量,会影响肺部炎症和肺功能的严重程度。饲养在更清洁、高屏障(HB)无特定病原体设施中的变应原-naive 动物,其肺部组织中的炎症细胞因子水平升高,免疫细胞浸润增加,但与饲养在卫生条件较差、低屏障无特定病原体设施中的动物相比,支气管肺泡灌洗液中没有这种情况。在两性中,HB 设施中的屋尘螨诱导的气道疾病比低屏障设施更为严重。在每个屏障设施中,雌性小鼠的炎症最为严重。然而,无论饲养环境如何,变应原-naive 雄性小鼠的肺功能都更差,在 HB 中,屋尘螨模型中雌性小鼠的肺功能更高。HB 中的严重疾病与肺部微生物组多样性减少有关。肺部微生物组在饲养屏障、性别和过敏原暴露组之间发生改变。因此,饲养屏障水平会影响过敏性哮喘中的微生物驱动疾病和性别表型。在更清洁的 HB 设施中饲养实验小鼠会加重肺部免疫,并导致更严重的过敏性肺部疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/907b/9404370/92a9d7d25471/nihms-1830822-f0001.jpg

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