Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19.
Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19.
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DOI：
10.1016/j.ebiom.2023.104945
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发表时间：
2024-01
期刊：
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
重症COVID-19的肺损伤具有高度异质性，但缺乏专门研究弥漫性肺泡损伤（DAD）离散时间期和交替肺损伤模式的空间区分。现有的研究也没有考虑到细胞密度估计中的渐进空域湮没。我们使用带有空域校正步骤的成像细胞计数（IMC）分析来更准确地识别支撑严重COVID-19肺部疾病异质性的细胞免疫反应。在COVID-19严重死亡病例的尸检中获得肺组织。病理学家选择的兴趣区域（roi）通过光学显微镜选择，代表DAD的病理进化谱，并选择替代疾病表型进行比较。结构上正常的sars - cov -2阳性肺组织和来自sars - cov -2阴性供者的组织作为对照。用40种细胞蛋白标记物对roi进行染色，用IMC进行消融，然后对分节的细胞进行分类。通过ROI空域校正的细胞群及其空间关系在肺损伤模式中进行了比较。40例患者（32M:8F，年龄：22-98），345例roi和bb90k单细胞进行分析。DAD的进展表现为空域闭塞，单核吞噬细胞（MnPs）、T淋巴细胞和B淋巴细胞显著增加，肺泡上皮细胞和内皮细胞显著减少。中性粒细胞总体上是稳定的，尽管一些对干扰素有反应的亚群表现出扩张。空间分析显示免疫细胞相互作用发生在显微镜下可察觉的组织损伤之前。COVID-19肺部疾病中严重DAD的免疫发病机制的特点是MnPs和淋巴细胞持续增加，甚至在肺损伤确定之前就发生了关键的相互作用。/通过，，，，，。
Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease. Lung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns. Forty patients (32M:8F, age: 22–98), 345 ROIs and >900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury. The immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established. / through the , , , , , .
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影响因子：
64.5
作者：
Hou, Yixuan J.;Okuda, Kenichi;Baric, Ralph S.
通讯作者：
Baric, Ralph S.
DOI：
10.1186/s13054-021-03492-x
发表时间：
2021-02-23
期刊：
Critical care (London, England)
影响因子：
--
作者：
Contou D;Cally R;Sarfati F;Desaint P;Fraissé M;Plantefève G
通讯作者：
Plantefève G
影响因子：
64.8
作者：
Delorey TM;Ziegler CGK;Heimberg G;Normand R;Yang Y;Segerstolpe Å;Abbondanza D;Fleming SJ;Subramanian A;Montoro DT;Jagadeesh KA;Dey KK;Sen P;Slyper M;Pita-Juárez YH;Phillips D;Biermann J;Bloom-Ackermann Z;Barkas N;Ganna A;Gomez J;Melms JC;Katsyv I;Normandin E;Naderi P;Popov YV;Raju SS;Niezen S;Tsai LT;Siddle KJ;Sud M;Tran VM;Vellarikkal SK;Wang Y;Amir-Zilberstein L;Atri DS;Beechem J;Brook OR;Chen J;Divakar P;Dorceus P;Engreitz JM;Essene A;Fitzgerald DM;Fropf R;Gazal S;Gould J;Grzyb J;Harvey T;Hecht J;Hether T;Jané-Valbuena J;Leney-Greene M;Ma H;McCabe C;McLoughlin DE;Miller EM;Muus C;Niemi M;Padera R;Pan L;Pant D;Pe'er C;Pfiffner-Borges J;Pinto CJ;Plaisted J;Reeves J;Ross M;Rudy M;Rueckert EH;Siciliano M;Sturm A;Todres E;Waghray A;Warren S;Zhang S;Zollinger DR;Cosimi L;Gupta RM;Hacohen N;Hibshoosh H;Hide W;Price AL;Rajagopal J;Tata PR;Riedel S;Szabo G;Tickle TL;Ellinor PT;Hung D;Sabeti PC;Novak R;Rogers R;Ingber DE;Jiang ZG;Juric D;Babadi M;Farhi SL;Izar B;Stone JR;Vlachos IS;Solomon IH;Ashenberg O;Porter CBM;Li B;Shalek AK;Villani AC;Rozenblatt-Rosen O;Regev A
通讯作者：
Regev A
影响因子：
17.1
作者：
Bharat A;Querrey M;Markov NS;Kim S;Kurihara C;Garza-Castillon R;Manerikar A;Shilatifard A;Tomic R;Politanska Y;Abdala-Valencia H;Yeldandi AV;Lomasney JW;Misharin AV;Budinger GRS
通讯作者：
Budinger GRS
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny