Comparative analysis of pulmonary immunopathology in COVID-19 patients and experimentally SARS-CoV-2 infected hamsters

Comparative analysis of pulmonary immunopathology in COVID-19 patients and experimentally SARS-CoV-2 infected hamsters
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DOI:
10.1016/j.jcpa.2023.03.029
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发表时间:
2023-06-10
影响因子:
0.8
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中科院分区:
农林科学4区
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材料与方法:对自然感染SARS-CoV-2的患者和实验感染的仓鼠(金黄地鼠)的福尔马林固定、石蜡包埋的肺组织进行了分析。在两种物种中表征形态学发现,并使用软件辅助图像分析管道在整个扫描载玻片上量化肺部病变。结果:在人和仓鼠中,SARS-CoV-2均以II型肺泡上皮细胞和巨噬细胞为靶点,免疫细胞浸润以巨噬细胞为主,II型肺泡上皮细胞增殖。在这两个物种的肺微环境的空间分析确定的邻居分析的差异。然而,在上皮细胞中的干扰素刺激的基因的蛋白质表达是共享之间的人类和仓鼠。结论:人类和仓鼠感染SARS冠状病毒-2显示出相似的轨迹在肺部免疫病理学的疾病途径。此外,在两个物种中检测到先天免疫反应的可比方面。因此,仓鼠是研究疾病发病机制的精美模型;然而,细胞微环境的一些细节在物种之间存在差异。
Materials and methods: Formalin-fixed, paraffin-embedded lung tissue of patients naturally infected with SARS-CoV-2 and experimentally infected hamsters (Mesocricetus auratus) were analysed. Morphological findings were characterized in both species and lung lesions quantified on whole scanned slides with software-assisted image analysis pipelines. The tissue microenvironment was studied with the PhenoCycler technology (Akoya).Results: In both humans and hamsters, SARS-CoV-2 was found to target type II pneumocytes and macrophages; immune cell infiltration is dominated by macrophages and proliferation of type II pneumocytes is present. The spatial analysis of the pulmonary microenvironment in both species identified differences in the neighbourhood analyses. However, protein expression of an interferon-stimulated gene in epithelial cells was shared between humans and hamsters.Conclusions: Humans and hamsters infected with SARS-CoV-2 show similar trajectories in the disease pathways of the lung immunopathology. In addition, comparable aspects of the innate immune response have been detected in both species. Hence, the hamster is an exquisite model to study disease pathogenesis; however, some details in the cellular microenvironment differ between the species.