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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\u2013inducing activation of brain cells and the subsequent neuroinflammation remain to be fully delineated. Our research, along with others\u2019, has recently demonstrated that SARS-CoV-2\u2013induced 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\u2013induced 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\u2013triggered 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\u2013induced neuroinflammation.<\/jats:p>","DOI":"10.3389\/fcimb.2024.1358873","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T05:04:08Z","timestamp":1712207048000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain microvascular endothelial cells and microglia"],"prefix":"10.3389","volume":"14","author":[{"given":"Meng-Li","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengzuo","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jincun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Hua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12987-022-00357-5","article-title":"Role of aging in Blood-Brain Barrier dysfunction and susceptibility to SARS-CoV-2 infection: impacts on neurological symptoms of COVID-19","volume":"19","author":"Adesse","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"B2","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s40478-020-01024-2","article-title":"Neuronophagia and microglial nodules in a SARS-CoV-2 patient with cerebellar hemorrhage","volume":"8","author":"Al-Dalahmah","year":"2020","journal-title":"Acta Neuropathol. 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