Novel insight into the underlying dysregulation mechanisms of immune cell-to-cell communication by analyzing multitissue single-cell atlas of two COVID-19 patients

• Published in: Cell death & disease Vol. 14; no. 4; p. 286
• Main Authors: Qin, Shijie, Yao, Xiaohong, Li, Weiwei, Wang, Canbiao, Xu, Weijun, Gan, Zhenhua, Yang, Yang, Zhong, Aifang, Wang, Bin, He, Zhicheng, Wu, Jian, Wu, Qiuyue, Jiang, Weijun, Han, Ying, Wang, Fan, Wang, Zhihua, Ke, Yuehua, Zhao, Jun, Gao, Junyin, Qu, Liang, Jin, Ping, Guan, Miao, Xia, Xinyi, Bian, Xiuwu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.04.2023; Springer Nature B.V; Nature Publishing Group
• Subjects: 13; 13/51; 38; 38/39; 45; 631/250/255/2514; 692/420/254; 96/95; Antibodies; Biochemistry; Biomedical and Life Sciences; Bone marrow; CC chemokine receptors; CCR1 protein; Cell activation; Cell Biology; Cell Communication; Cell Culture; Cell interactions; Communication; Coronaviruses; COVID-19; Fibroblasts; Fibrosis; Humans; Immunology; Inflammation; Life Sciences; Ligands; Lung; Lung diseases; Lungs; Lymphocytes T; Myeloid cells; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Transcriptomes
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-023-05814-z

How does SARS-CoV-2 cause lung microenvironment disturbance and inflammatory storm is still obscure. We here performed the single-cell transcriptome sequencing from lung, blood, and bone marrow of two dead COVID-19 patients and detected the cellular communication among them. Our results demonstrated that SARS-CoV-2 infection increase the frequency of cellular communication between alveolar type I cells (AT1) or alveolar type II cells (AT2) and myeloid cells triggering immune activation and inflammation microenvironment and then induce the disorder of fibroblasts, club, and ciliated cells, which may cause increased pulmonary fibrosis and mucus accumulation. Further study showed that the increase of T cells in the lungs may be mainly recruited by myeloid cells through ligands/receptors (e.g., ANXA1/FPR1, C5AR1/RPS19, and CCL5/CCR1). Interestingly, we also found that certain ligands/receptors (e.g., ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1) are significantly activated and shared among lungs, blood and bone marrow of COVID-19 patients, implying that the dysregulation of ligands/receptors may lead to immune cell’s activation, migration, and the inflammatory storm in different tissues of COVID-19 patients. Collectively, our study revealed a possible mechanism by which the disorder of cell communication caused by SARS-CoV-2 infection results in the lung inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.