Mast cell activation triggered by SARS-CoV-2 causes inflammation in brain microvascular endothelial cells and microglia

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.

Preliminary Analysis of Aging-Related Genes in Intracerebral Hemorrhage by Integration of Bulk and Single-Cell RNA Sequencing Technology

“…It suggested that these aging-related genes could play an important role in activated mast cell-mediated damage to blood–brain barrier, providing novel therapeutic targets for ICH. Mast cell-mediated endothelial injury is prevalent in the central nervous system, 70 respiratory system, 71 cardiovascular system, 72 and intestinal system. 73 Previous research has demonstrated that mast cells can trigger inflammatory responses in human cerebral microvascular endothelial cells through degranulation, leading to disruption of the blood–brain barrier (BBB) during neurological inflammation caused by ICH.…”