The spatial landscape of lung pathology during COVID-19 progression.
The spatial landscape of lung pathology during COVID-19 progression.
复制标题
新冠病毒感染（COVID-19）进展过程中肺部病变的空间景观。
DOI：
10.1038/s41586-021-03475-6
复制
发表时间：
2021-05
期刊：
影响因子：
64.8
通讯作者：
Schwartz RE
中科院分区：
文献类型：
--
作者：
Rendeiro AF;Ravichandran H;Bram Y;Chandar V;Kim J;Meydan C;Park J;Foox J;Hether T;Warren S;Kim Y;Reeves J;Salvatore S;Mason CE;Swanson EC;Borczuk AC;Elemento O;Schwartz RE
最近的研究为COVID-19的病理学和免疫反应提供了见解。然而，对感染细胞和免疫系统在感染部位之间的相互作用缺乏彻底的调查。在这里，我们使用高参数成像质谱细胞术，靶向36种蛋白质的表达，以单细胞分辨率研究人类急性肺损伤（包括SARS-CoV-2感染引起的损伤）的细胞组成和空间结构。这些空间分辨的单细胞数据揭示了感染和损伤肺的无序结构，以及广泛的免疫浸润的分布。中性粒细胞和巨噬细胞浸润分别是细菌性肺炎和COVID-19的标志。我们提供的证据表明，SARS-CoV-2感染主要是肺泡上皮细胞，并诱导局部高度炎症细胞状态，这与肺损伤有关。我们利用COVID-19致命结果与症状发作相关的时间范围，这揭示了随着疾病进展，巨噬细胞外渗增加，间充质细胞和成纤维细胞数量增加，伴随着这些细胞类型之间的接近度增加-可能是试图修复受损肺组织的结果。我们的数据使我们能够从结构、免疫学和临床角度开发出一种生物学上可解释的肺部病理学景观。我们利用这一景观来表征人类肺部的病理生理学，从其宏观表现到单细胞水平，这为理解COVID-19和肺部病理学提供了重要基础。
Recent studies have provided insights into the pathology of and immune response to COVID-19. However, a thorough investigation of the interplay between infected cells and the immune system at sites of infection has been lacking. Here we use high-parameter imaging mass cytometry that targets the expression of 36 proteins to investigate the cellular composition and spatial architecture of acute lung injury in humans (including injuries derived from SARS-CoV-2 infection) at single-cell resolution. These spatially resolved single-cell data unravel the disordered structure of the infected and injured lung, alongside the distribution of extensive immune infiltration. Neutrophil and macrophage infiltration are hallmarks of bacterial pneumonia and COVID-19, respectively. We provide evidence that SARS-CoV-2 infects predominantly alveolar epithelial cells and induces a localized hyperinflammatory cell state that is associated with lung damage. We leverage the temporal range of fatal outcomes of COVID-19 in relation to the onset of symptoms, which reveals increased macrophage extravasation and increased numbers of mesenchymal cells and fibroblasts concomitant with increased proximity between these cell types as the disease progresses—possibly as a result of attempts to repair the damaged lung tissue. Our data enable us to develop a biologically interpretable landscape of lung pathology from a structural, immunological and clinical standpoint. We use this landscape to characterize the pathophysiology of the human lung from its macroscopic presentation to the single-cell level, which provides an important basis for understanding COVID-19 and lung pathology in general.
登录
查看更多内容
DOI：
10.1146/annurev-pathol-020712-163930
发表时间：
2013-01-24
期刊：
Annual review of pathology
影响因子：
--
作者：
Duffield JS;Lupher M;Thannickal VJ;Wynn TA
通讯作者：
Wynn TA
影响因子：
9.8
作者：
McQuin C;Goodman A;Chernyshev V;Kamentsky L;Cimini BA;Karhohs KW;Doan M;Ding L;Rafelski SM;Thirstrup D;Wiegraebe W;Singh S;Becker T;Caicedo JC;Carpenter AE
通讯作者：
Carpenter AE
影响因子：
64.8
作者：
Harris CR;Millman KJ;van der Walt SJ;Gommers R;Virtanen P;Cournapeau D;Wieser E;Taylor J;Berg S;Smith NJ;Kern R;Picus M;Hoyer S;van Kerkwijk MH;Brett M;Haldane A;Del Río JF;Wiebe M;Peterson P;Gérard-Marchant P;Sheppard K;Reddy T;Weckesser W;Abbasi H;Gohlke C;Oliphant TE
通讯作者：
Oliphant TE
DOI：
10.1016/s2213-2600(20)30370-2
发表时间：
2020-12
期刊：
The Lancet. Respiratory medicine
影响因子：
--
作者：
Grasselli G;Tonetti T;Protti A;Langer T;Girardis M;Bellani G;Laffey J;Carrafiello G;Carsana L;Rizzuto C;Zanella A;Scaravilli V;Pizzilli G;Grieco DL;Di Meglio L;de Pascale G;Lanza E;Monteduro F;Zompatori M;Filippini C;Locatelli F;Cecconi M;Fumagalli R;Nava S;Vincent JL;Antonelli M;Slutsky AS;Pesenti A;Ranieri VM;collaborators
通讯作者：
collaborators
影响因子：
48
作者：
Giesen, Charlotte;Wang, Hao A. O.;Bodenmiller, Bernd
通讯作者：
Bodenmiller, Bernd