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

Front Cell Infect Microbiol. 2024 Apr 4:14:1358873. doi: 10.3389/fcimb.2024.1358873. eCollection 2024.

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.

Keywords: SARS-CoV-2; degranulation; mast cell; neuroinflammation; tight junction protein.

MeSH terms

  • Animals
  • Brain / metabolism
  • COVID-19* / metabolism
  • Cytokines / metabolism
  • Endothelial Cells / metabolism
  • Humans
  • Inflammation / metabolism
  • Mast Cells / metabolism
  • Mice
  • Microglia / metabolism
  • Neuroinflammatory Diseases
  • SARS-CoV-2* / metabolism

Substances

  • Cytokines

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (82172242), the Natural Science Foundation of Guangdong (2022A1515012053), and the State key Laboratory of Respiratory Disease, Guangzhou, China (SKLRD-OP202207). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.