tetano
Editor, Senior Moderator
Cell Discov
. 2020 Oct 20;6:73.
doi: 10.1038/s41421-020-00225-2. eCollection 2020.
The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing
Gang Xu[SUP] #[/SUP][SUP] 1 [/SUP], Furong Qi[SUP] #[/SUP][SUP] 1 [/SUP], Hanjie Li[SUP] #[/SUP][SUP] 2 [/SUP], Qianting Yang[SUP] 1 [/SUP], Haiyan Wang[SUP] 1 [/SUP], Xin Wang[SUP] 1 [/SUP], Xiaoju Liu[SUP] 3 [/SUP], Juanjuan Zhao[SUP] 1 [/SUP], Xuejiao Liao[SUP] 1 [/SUP], Yang Liu[SUP] 1 [/SUP], Lei Liu[SUP] 1 [/SUP], Shuye Zhang[SUP] 4 [/SUP], Zheng Zhang[SUP] 1 [/SUP]
Affiliations
Abstract
Understanding the mechanism that leads to immune dysfunction in severe coronavirus disease 2019 (COVID-19) is crucial for the development of effective treatment. Here, using single-cell RNA sequencing, we characterized the peripheral blood mononuclear cells (PBMCs) from uninfected controls and COVID-19 patients and cells in paired broncho-alveolar lavage fluid (BALF). We found a close association of decreased dendritic cells (DCs) and increased monocytes resembling myeloid-derived suppressor cells (MDSCs), which correlated with lymphopenia and inflammation in the blood of severe COVID-19 patients. Those MDSC-like monocytes were immune-paralyzed. In contrast, monocyte-macrophages in BALFs of COVID-19 patients produced massive amounts of cytokines and chemokines, but secreted little interferons. The frequencies of peripheral T cells and NK cells were significantly decreased in severe COVID-19 patients, especially for innate-like T and various CD8[SUP]+[/SUP] T cell subsets, compared to healthy controls. In contrast, the proportions of various activated CD4[SUP]+[/SUP] T cell subsets among the T cell compartment, including Th1, Th2, and Th17-like cells were increased and more clonally expanded in severe COVID-19 patients. Patients' peripheral T cells showed no sign of exhaustion or augmented cell death, whereas T cells in BALFs produced higher levels of IFNG, TNF, CCL4, CCL5, etc. Paired TCR tracking indicated abundant recruitment of peripheral T cells to the severe patients' lung. Together, this study comprehensively depicts how the immune cell landscape is perturbed in severe COVID-19.
Keywords: Bioinformatics; Immunology.
. 2020 Oct 20;6:73.
doi: 10.1038/s41421-020-00225-2. eCollection 2020.
The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing
Gang Xu[SUP] #[/SUP][SUP] 1 [/SUP], Furong Qi[SUP] #[/SUP][SUP] 1 [/SUP], Hanjie Li[SUP] #[/SUP][SUP] 2 [/SUP], Qianting Yang[SUP] 1 [/SUP], Haiyan Wang[SUP] 1 [/SUP], Xin Wang[SUP] 1 [/SUP], Xiaoju Liu[SUP] 3 [/SUP], Juanjuan Zhao[SUP] 1 [/SUP], Xuejiao Liao[SUP] 1 [/SUP], Yang Liu[SUP] 1 [/SUP], Lei Liu[SUP] 1 [/SUP], Shuye Zhang[SUP] 4 [/SUP], Zheng Zhang[SUP] 1 [/SUP]
Affiliations
- PMID: 33101705
- PMCID: PMC7574992
- DOI: 10.1038/s41421-020-00225-2
Abstract
Understanding the mechanism that leads to immune dysfunction in severe coronavirus disease 2019 (COVID-19) is crucial for the development of effective treatment. Here, using single-cell RNA sequencing, we characterized the peripheral blood mononuclear cells (PBMCs) from uninfected controls and COVID-19 patients and cells in paired broncho-alveolar lavage fluid (BALF). We found a close association of decreased dendritic cells (DCs) and increased monocytes resembling myeloid-derived suppressor cells (MDSCs), which correlated with lymphopenia and inflammation in the blood of severe COVID-19 patients. Those MDSC-like monocytes were immune-paralyzed. In contrast, monocyte-macrophages in BALFs of COVID-19 patients produced massive amounts of cytokines and chemokines, but secreted little interferons. The frequencies of peripheral T cells and NK cells were significantly decreased in severe COVID-19 patients, especially for innate-like T and various CD8[SUP]+[/SUP] T cell subsets, compared to healthy controls. In contrast, the proportions of various activated CD4[SUP]+[/SUP] T cell subsets among the T cell compartment, including Th1, Th2, and Th17-like cells were increased and more clonally expanded in severe COVID-19 patients. Patients' peripheral T cells showed no sign of exhaustion or augmented cell death, whereas T cells in BALFs produced higher levels of IFNG, TNF, CCL4, CCL5, etc. Paired TCR tracking indicated abundant recruitment of peripheral T cells to the severe patients' lung. Together, this study comprehensively depicts how the immune cell landscape is perturbed in severe COVID-19.
Keywords: Bioinformatics; Immunology.