Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury

Jian-Bo Cao; Shu-Tong Zhu; Xiao-Shan Huang; Xing-Yuan Wang; Meng-Li Wu; Xin Li; Feng-Liang Liu; Ling Chen; Yong-Tang Zheng; Jian-Hua Wang

doi:10.1016/j.virs.2024.03.001

April 2024

Citation: Jian-Bo Cao, Shu-Tong Zhu, Xiao-Shan Huang, Xing-Yuan Wang, Meng-Li Wu, Xin Li, Feng-Liang Liu, Ling Chen, Yong-Tang Zheng, Jian-Hua Wang. Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury .VIROLOGICA SINICA, 2024, 39(2) : 309-318. http://dx.doi.org/10.1016/j.virs.2024.03.001

Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury

Jian-Bo Cao ^a,b ,
Shu-Tong Zhu ^a ,
Xiao-Shan Huang ^a ,
Xing-Yuan Wang ^a ,
Meng-Li Wu ^a ,
Xin Li ^a ,
Feng-Liang Liu ^c ,
Ling Chen ^a ,
Yong-Tang Zheng ^{c
,,} ,
Jian-Hua Wang ^{a,d
,,}

a. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China;
b. School of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China;
c. Key Laboratory of Bioactive Peptides of Yunnan Province, Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China;
d. University of Chinese Academy of Sciences, Beijing 101408, China

Corresponding author: Yong-Tang Zheng, zhengyt@mail.kiz.ac.cn
Jian-Hua Wang, wang_jianhua@gibh.ac.cn
Received Date: 11 August 2023
Accepted Date: 27 February 2024
Available online: 06 March 2024

Abstract

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others', has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells, leading to subsequent lung injury. The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation, and inflammation in these regions could promote viral spread. MCs are widely distributed throughout the respiratory tract. Thus, in this study, we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium. Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2. MC degranulation caused lesions in trachea, and the formation of papillary hyperplasia was observed. Through transcriptome analysis in bronchial epithelial cells, we found that MC degranulation significantly altered multiple cellular signaling, particularly, leading to upregulated immune responses and inflammation. The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice. Taken together, our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions. Furthermore, our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation, thereby preventing tissue damage caused by hyper-inflammation.
- SARS-CoV-2
- , Mast cell (MC)
- , Bronchial epithelial cell
- , Inflammation
- , Tracheal injury

Electronic Supplementary Material

10.1016j.virs.2024.03.001-ESM.docx
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