Human nasal wash RNA-Seq reveals distinct cell-specific innate immune responses in influenza versus SARS-CoV-2

被引:17
|
作者
Gao, Kevin M. [1 ]
Derr, Alan G. [2 ]
Guo, Zhiru [1 ]
Nundel, Kerstin [1 ]
Marshak-Rothstein, Ann [1 ]
Finberg, Robert W. [1 ]
Wang, Jennifer P. [1 ]
机构
[1] Univ Massachusetts, Chan Med Sch, Dept Med, Worcester, MA 01605 USA
[2] Univ Massachusetts, Dept Bioinformat & Integrat Biol, Chan Med Sch, Worcester, MA 01605 USA
关键词
COVID-19; INFECTION; MORTALITY; SEVERITY;
D O I
10.1172/jci.insight.152288
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
BACKGROUND. Influenza A virus (IAV) and SARS-CoV-2 are pandemic viruses causing millions of deaths, yet their clinical manifestations are distinctly different. METHODS. With the hypothesis that upper airway immune and epithelial cell responses are also distinct, we performed single-cell RNA sequencing (scRNA-Seq) on nasal wash cells freshly collected from adults with either acute COVID-19 or influenza or from healthy controls. We focused on major cell types and subtypes in a subset of donor samples. RESULTS. Nasal wash cells were enriched for macrophages and neutrophils for both individuals with influenza and those with COVID-19 compared with healthy controls. Hillock-like epithelial cells, M2-like macrophages, and age-dependent B cells were enriched in COVID-19 samples. A global decrease in IFN-associated transcripts in neutrophils, macrophages, and epithelial cells was apparent in COVID-19 samples compared with influenza samples. The innate immune response to SARS-CoV-2 appears to be maintained in macrophages, despite evidence for limited epithelial cell immune sensing. Cell-to-cell interaction analyses revealed a decrease in epithelial cell interactions in COVID-19 and highlighted differences in macrophage-macrophage interactions for COVID-19 and influenza. CONCLUSIONS. Our study demonstrates that scRNA-Seq can define host and viral transcriptional activity at the site of infection and reveal distinct local epithelial and immune cell responses for COVID-19 and influenza that may contribute to their divergent disease courses.
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页数:15
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