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

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. Youngblood*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number650331
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - Mar 10 2021

Keywords

  • COVID-19
  • SARS-CoV-2
  • Siglec-8
  • Toll-like receptor
  • eosinophil
  • lirentelimab
  • mast cell
  • viral inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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