Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection represents a global health crisis. Immune cell activation via pattern recognition receptors has been implicated as a driver of the hyperinflammatory response seen in COVID-19. However, our understanding of the specific immune responses to SARS-CoV-2 remains limited. Mast cells (MCs) and eosinophils are innate immune cells that play pathogenic roles in many inflammatory responses. Here we report MC-derived proteases and eosinophil-associated mediators are elevated in COVID-19 patient sera and lung tissues. Stimulation of viral-sensing toll-like receptors in vitro and administration of synthetic viral RNA in vivo induced features of hyperinflammation, including cytokine elevation, immune cell airway infiltration, and MC-protease production—effects suppressed by an anti-Siglec-8 monoclonal antibody which selectively inhibits MCs and depletes eosinophils. Similarly, anti-Siglec-8 treatment reduced disease severity and airway inflammation in a respiratory viral infection model. These results suggest that MC and eosinophil activation are associated with COVID-19 inflammation and anti-Siglec-8 antibodies are a potential therapeutic approach for attenuating excessive inflammation during viral infections.
【저자키워드】 COVID-19, SARS-CoV-2, Toll-like receptor, mast cell, eosinophil, Siglec-8, lirentelimab, viral inflammation, 【초록키워드】 Treatment, coronavirus disease, Inflammation, viral infection, Coronavirus disease 2019, immune response, Inflammatory responses, antibody, SARS-COV-2 infection, disease severity, monoclonal antibody, cytokine, protease, in vitro, viral infections, eosinophil, Health crisis, airway, Pattern recognition, Health, Viral, eosinophils, immune responses, sera, hyperinflammation, immune cells, Pattern recognition receptors, Innate immune cells, Viral RNA, Proteases, respiratory, in vivo, respiratory viral infection, Mast cells, Stimulation, Hyperinflammatory response, infiltration, administration, Therapeutic approach, Immune cell, COVID-19 patient, pattern recognition receptor, mediators, Activation, Airway inflammation, excessive inflammation, pathogenic, cell activation, lung tissues, Hyperinflammatory, feature, caused, inhibit, elevated, reduced, suppressed, implicated, deplete, innate immune cell, MCs, with COVID-19, 【제목키워드】 mast cell,