Mast Cell and Eosinophil Activation Are Associated With COVID-19 and TLR-Mediated Viral Inflammation: Implications for an Anti-Siglec-8 Antibody

• DOI: 10.3389/fimmu.2021.650331
• Publication Date: 2021-03-10T06:08:02Z
• Authors: Simon Gebremeskel; Julia Schanin; Krysta M. Coyle; Melina Butuci; Thuy Luu; Emily C. Brock; Alan Xu; Alan Wong; John Leung; Wouter Korver; Ryan D. Morin; Robert P. Schleimer; Bruce S. Bochner; Bradford A. Young...
• Keywords: 0301 basic medicine; Immunology; Mice, Transgenic; Respiratory Syncytial Virus Infections; 03 medical and health sciences; Toll-like receptor; Antigens, CD; Lectins; Animals; Humans; eosinophil; Mast Cells; SARS-CoV-2; Toll-Like Receptors; Siglec-8; Antibodies, Monoclonal; COVID-19; RC581-607; Respiratory Syncytial Viruses; 3. Good health; Antigens, Differentiation, B-Lymphocyte; Eosinophils; Disease Models, Animal; Case-Control Studies; Host-Pathogen Interactions; Cytokines; Immunologic diseases. Allergy; mast cell; Peptide Hydrolases

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 receptorsin vitroand administration of synthetic viral RNAin vivoinduced 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.