Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain microvascular endothelial cells and microglia
SARS-CoV-2–induced excessive inflammation in brain leads to damage of blood–brain barrier, hypoxic-ischemic injury, and neuron degeneration. The production of inflammatory cytokines by brain microvascular endothelial cells and microglia is reported to be critically associated with the brain patholog...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1358873/full |
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| author | Meng-Li Wu Chengzuo Xie Chengzuo Xie Xin Li Jing Sun Jincun Zhao Jian-Hua Wang Jian-Hua Wang Jian-Hua Wang |
| author_facet | Meng-Li Wu Chengzuo Xie Chengzuo Xie Xin Li Jing Sun Jincun Zhao Jian-Hua Wang Jian-Hua Wang Jian-Hua Wang |
| author_sort | Meng-Li Wu |
| collection | DOAJ |
| description | SARS-CoV-2–induced excessive inflammation in brain leads to damage of blood–brain barrier, hypoxic-ischemic injury, and neuron degeneration. The production of inflammatory cytokines by brain microvascular endothelial cells and microglia is reported to be critically associated with the brain pathology of COVID-19 patients. However, the cellular mechanisms for SARS-CoV-2–inducing activation of brain cells and the subsequent neuroinflammation remain to be fully delineated. Our research, along with others’, has recently demonstrated that SARS-CoV-2–induced accumulation and activation of mast cells (MCs) in mouse lung could further induce inflammatory cytokines and consequent lung damages. Intracerebral MCs activation and their cross talk with other brain cells could induce neuroinflammation that play important roles in neurodegenerative diseases including virus-induced neuro-pathophysiology. In this study, we investigated the role of MC activation in SARS-CoV-2–induced neuroinflammation. We found that (1) SARS-CoV-2 infection triggered MC accumulation in the cerebrovascular region of mice; (2) spike/RBD (receptor-binding domain) protein–triggered MC activation induced inflammatory factors in human brain microvascular endothelial cells and microglia; (3) MC activation and degranulation destroyed the tight junction proteins in brain microvascular endothelial cells and induced the activation and proliferation of microglia. These findings reveal a cellular mechanism of SARS-CoV-2–induced neuroinflammation. |
| first_indexed | 2024-04-24T13:51:11Z |
| format | Article |
| id | doaj.art-220fcee573694107b79d81f16d80770e |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-24T13:51:11Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-220fcee573694107b79d81f16d80770e2024-04-04T05:03:05ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882024-04-011410.3389/fcimb.2024.13588731358873Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain microvascular endothelial cells and microgliaMeng-Li Wu0Chengzuo Xie1Chengzuo Xie2Xin Li3Jing Sun4Jincun Zhao5Jian-Hua Wang6Jian-Hua Wang7Jian-Hua Wang8Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaGuangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaGuangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaSARS-CoV-2–induced excessive inflammation in brain leads to damage of blood–brain barrier, hypoxic-ischemic injury, and neuron degeneration. The production of inflammatory cytokines by brain microvascular endothelial cells and microglia is reported to be critically associated with the brain pathology of COVID-19 patients. However, the cellular mechanisms for SARS-CoV-2–inducing activation of brain cells and the subsequent neuroinflammation remain to be fully delineated. Our research, along with others’, has recently demonstrated that SARS-CoV-2–induced accumulation and activation of mast cells (MCs) in mouse lung could further induce inflammatory cytokines and consequent lung damages. Intracerebral MCs activation and their cross talk with other brain cells could induce neuroinflammation that play important roles in neurodegenerative diseases including virus-induced neuro-pathophysiology. In this study, we investigated the role of MC activation in SARS-CoV-2–induced neuroinflammation. We found that (1) SARS-CoV-2 infection triggered MC accumulation in the cerebrovascular region of mice; (2) spike/RBD (receptor-binding domain) protein–triggered MC activation induced inflammatory factors in human brain microvascular endothelial cells and microglia; (3) MC activation and degranulation destroyed the tight junction proteins in brain microvascular endothelial cells and induced the activation and proliferation of microglia. These findings reveal a cellular mechanism of SARS-CoV-2–induced neuroinflammation.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1358873/fullSARS-CoV-2mast cellneuroinflammationtight junction proteindegranulation |
| spellingShingle | Meng-Li Wu Chengzuo Xie Chengzuo Xie Xin Li Jing Sun Jincun Zhao Jian-Hua Wang Jian-Hua Wang Jian-Hua Wang Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain microvascular endothelial cells and microglia Frontiers in Cellular and Infection Microbiology SARS-CoV-2 mast cell neuroinflammation tight junction protein degranulation |
| title | Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain microvascular endothelial cells and microglia |
| title_full | Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain microvascular endothelial cells and microglia |
| title_fullStr | Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain microvascular endothelial cells and microglia |
| title_full_unstemmed | Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain microvascular endothelial cells and microglia |
| title_short | Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain microvascular endothelial cells and microglia |
| title_sort | mast cell activation triggered by sars cov 2 causes inflammation in brain microvascular endothelial cells and microglia |
| topic | SARS-CoV-2 mast cell neuroinflammation tight junction protein degranulation |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1358873/full |
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