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Isolating Central Nervous System Tissues and Associated Meninges for the Downstream Analysis of Immune cells
Published on: May 19, 2020
Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain microvascular endothelial cells and
Meng-Li Wu1, Chengzuo Xie1,2, Xin Li1
1Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Abstract:
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.
Insights
SARS-CoV-2 infection activates brain mast cells (MCs), leading to neuroinflammation. This activation damages the blood-brain barrier and affects brain cells, contributing to COVID-19 brain pathology.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- SARS-CoV-2 causes brain inflammation, blood-brain barrier damage, and neuron degeneration.
- Brain microvascular endothelial cells and microglia produce inflammatory cytokines linked to COVID-19 brain pathology.
- Cellular mechanisms of SARS-CoV-2-induced neuroinflammation are not fully understood.
Purpose of the Study:
- Investigate the role of mast cell (MC) activation in SARS-CoV-2-induced neuroinflammation.
- Elucidate the cellular mechanisms by which SARS-CoV-2 triggers brain cell activation and neuroinflammation.
Main Methods:
- Examined SARS-CoV-2 infection in mouse models.
- Assessed MC accumulation in the cerebrovascular region.
- Investigated the effects of spike/receptor-binding domain (RBD) protein on human brain microvascular endothelial cells and microglia.
- Analyzed tight junction proteins and microglial activation.
Main Results:
- SARS-CoV-2 infection led to MC accumulation in mouse brain vasculature.
- Spike/RBD protein-induced MC activation released inflammatory factors in brain endothelial cells and microglia.
- MC activation and degranulation disrupted tight junction proteins in brain microvascular endothelial cells.
- MC activation promoted microglial activation and proliferation.
Conclusions:
- Mast cell activation is a key mechanism in SARS-CoV-2-induced neuroinflammation.
- SARS-CoV-2 spike protein can directly trigger MCs, leading to brain cell damage and inflammatory responses.
- Findings reveal a cellular pathway contributing to COVID-19-related neurological complications.
