Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection.
Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection.
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DOI：
10.3390/cells11121864
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发表时间：
2022-06-07
期刊：
影响因子：
6
通讯作者：
Polverino, Francesca
中科院分区：
文献类型：
--
作者：
Yang, Chen Xi;Tomchaney, Michael;Landecho, Manuel F.;Zamacona, Borja R.;Oto, Marta Marin;Zulueta, Javier;Malo, Joshua;Knoper, Steve;Contoli, Marco;Papi, Alberto;Vasilescu, Dragos M.;Sauler, Maor;Straub, Christof;Tan, Cheryl;Martinez, Fernando D.;Bhattacharya, Deepta;Rosas, Ivan O.;Kheradmand, Farrah;Hackett, Tillie-Louise;Polverino, Francesca
患有慢性阻塞性肺疾病（COPD）等肺部疾病的人更有可能因2019年SARS-CoV-2疾病（COVID-19）而病情严重。尽管如此，对COPD患者对COVID-19感染的免疫反应（在空间上贯穿整个肺部结构）的研究仍然缺乏。在这项研究中，我们利用空间转录组学和蛋白质组学分析表征了非吸烟者和非吸烟者的肺组织、气道和血管的免疫微环境，这些患者均死于COVID-19。与对照肺相比，COPD患者的肺实质、气道和血管(1)肺常驻CD45RO+记忆性CD4+ T细胞显著富集；(2)与T细胞抗原启动和记忆T细胞分化相关的基因下调；(3)尽管SARS-CoV-2结构基因表达水平相似，但与SARS-CoV-2进入和主要受体相关的蛋白质在整个roi（特别是肺实质）中普遍表达更高。综上所述，COPD患者的肺实质、气道和血管中T淋巴细胞增加，CD4 T细胞反应减弱，SARS-CoV-2感染模式更具侵袭性，这可能是COVID-19死亡率较高的原因。
People with pre-existing lung diseases such as chronic obstructive pulmonary disease (COPD) are more likely to get very sick from SARS-CoV-2 disease 2019 (COVID-19). Still, an interrogation of the immune response to COVID-19 infection, spatially throughout the lung structure, is lacking in patients with COPD. For this study, we characterized the immune microenvironment of the lung parenchyma, airways, and vessels of never- and ever-smokers with or without COPD, all of whom died of COVID-19, using spatial transcriptomic and proteomic profiling. The parenchyma, airways, and vessels of COPD patients, compared to control lungs had (1) significant enrichment for lung-resident CD45RO+ memory CD4+ T cells; (2) downregulation of genes associated with T cell antigen priming and memory T cell differentiation; and (3) higher expression of proteins associated with SARS-CoV-2 entry and primary receptor ubiquitously across the ROIs and in particular the lung parenchyma, despite similar SARS-CoV-2 structural gene expression levels. In conclusion, the lung parenchyma, airways, and vessels of COPD patients have increased T-lymphocytes with a blunted memory CD4 T cell response and a more invasive SARS-CoV-2 infection pattern and may underlie the higher death toll observed with COVID-19.
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