应用成像质谱法确定covid -19感染后肺解剖组织中共定位病毒和免疫细胞浸润的n -聚糖谱

E. Jones, R. Drake, James W Dressman, Vaunita Parihar, Rachel Stubler, E. Masters, K. Mercer
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引用次数: 0

摘要

当前COVID-19大流行的特点是患者的疾病严重程度范围广泛。这种临床表现的多样性使我们对SARS-CoV-2发病机制的理解复杂化,并强调了个体发起有效病毒免疫反应能力的重要性。糖基化是复杂生物体中常见的翻译后修饰,对免疫细胞功能至关重要。本研究采用免疫组织化学(IHC)和基质辅助激光解吸/电离成像质谱(MALDI-IMS)相结合的方法,测定了COVID-19肺组织中n -聚糖和免疫细胞群的空间分布。分析了7例SARS-CoV-2、PCR +供体的组织。组织代表了在呼吸机上花费的时间谱,这反映在他们各自的病毒感染状态和肺部病理上。MALDI-IMS图像中的n -聚糖分布与SARS-CoV-2刺突蛋白、CD4、CD8、CD163和CD11b的H&E染色和IHC相关。在特定的免疫细胞类型及其与病毒刺突蛋白的共定位中,发现了不同的和共享的n -聚糖特征。此外,我们观察到α2,3-链和α2,6-链唾液酸聚糖的独特模式,它们与免疫细胞群和组织结构中的纤维化区域相关。n -聚糖MALDI-IMS是进一步了解组织定位免疫细胞群对新出现的病毒病原体(如SARS-CoV-2)反应的有效工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Applying imaging mass spectrometry to define the N-glycan profiles of co-localized virus and immune cell infiltrates in post-COVID-19 infected lung autopsy tissues
The current COVID-19 pandemic is characterized by a broad range of disease severity in patients. This diversity in clinical manifestations has complicated our understanding of the SARS-CoV-2 pathogenesis and highlights the significance of an individual’s ability to mount an effective viral immune response. Glycosylation is a common post-translational modification occurring in complex organisms and is imperative for immune cell function. In this study, a combination approach with immunohistochemistry (IHC) and matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) was utilized to determine the spatial distribution of N-glycans and immune cell populations in COVID-19 lung tissues. Tissues from seven SARS-CoV-2, PCR + donors were analyzed. Tissues represented a spectrum of time spent on ventilators which was reflected in their respective viral infection status and lung pathologies. N-glycan distributions in the MALDI-IMS images were then correlated with H&E staining and IHC of SARS-CoV-2 spike protein, CD4, CD8, CD163 and CD11b. Distinct and shared N-glycan signatures were identified in association with specific immune cell types, and their co-localization with the viral spike protein. Additionally, we observed unique patterns of α2,3-linked and α2,6-linked sialic acid glycans that associated with both immune cell populations and fibrotic regions within the tissue architecture. N-glycan MALDI-IMS is an effective tool to further understand tissue-localized immune cell populations in response to emerging viral pathogens such as SARS-CoV-2.
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