Mast cells promote viral entry of SARS-CoV-2 via formation of chymase/spike protein complex

The pulmonary pathological findings associated with severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) result from the release of multiple proinflammatory cytokines, which causes the subsequential damage of the lungs. The current study was undertaken to investigate the responses of mast cells to viral inoculation and their contribution to host defenses from the point of view of viral entry. Pseudovirions, in which the spike glycoprotein of SARS-CoV-2 was incorporated, triggered activation of mast cells, and a mast cell-derived chymase, MCP2, formed a complex with spike protein, which promoted protease-dependent viral entry. According to the quantification results of viral entry, 10 mu M quercetin, a mast cell stabilizer, potentially potently inhibited 41.3% of viral entry, while 100 mu M chymostatin, which served as a chymase inhibitor, suppressed 52.1% of viral entry, compared to non-treated cells. Study using mast cell-deficient mice showed that the absence of mast cells may influence early viral loading in the upper respiratory tract, which consequently increases the risk of viral invasion into the lower respiratory system. Furthermore, mast cell-deficient mice exhibited ongoing infection in the late phase post-viral inoculation, while clearance of virus-positive cells was observed in wild-type mice. In conclusion, mast cells act as a multifaceted immune modulator that is equipped with both protective effects and pathogenic influences on viral entry of SARS-CoV-2. The utility of mast cell stabilizers and chymase inhibitors in the treatment of SARS-CoV-2-induced acute respiratory syndrome should be optimized regarding the infection stage and the risk of cytokine storm.

Automated summary

This study investigated the role of mast cells in the response to SARS-CoV-2 viral inoculation and their contribution to host defenses. The results showed that mast cell stabilizers and chymase inhibitors have potential inhibitory effects on viral entry. Mast cell deficiency may increase the risk of viral invasion into the lower respiratory system.