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

Front Immunol. 2021 Mar 10;12:650331. doi: 10.3389/fimmu.2021.650331. eCollection 2021.

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.

Keywords: COVID-19; SARS-CoV-2; Siglec-8; Toll-like receptor; eosinophil; lirentelimab; mast cell; viral inflammation.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Antigens, Differentiation, B-Lymphocyte / genetics
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • Antigens, Differentiation, B-Lymphocyte / metabolism
  • COVID-19 / immunology*
  • COVID-19 / metabolism
  • COVID-19 / prevention & control
  • COVID-19 / virology
  • Case-Control Studies
  • Cytokines / metabolism
  • Disease Models, Animal
  • Eosinophils / drug effects
  • Eosinophils / immunology*
  • Eosinophils / metabolism
  • Eosinophils / virology
  • Host-Pathogen Interactions
  • Humans
  • Lectins / antagonists & inhibitors
  • Lectins / genetics
  • Lectins / immunology*
  • Lectins / metabolism
  • Mast Cells / drug effects
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Mast Cells / virology
  • Mice, Transgenic
  • Peptide Hydrolases / metabolism
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / metabolism
  • Respiratory Syncytial Virus Infections / prevention & control
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Viruses / immunology*
  • SARS-CoV-2 / immunology*
  • Toll-Like Receptors / immunology*
  • Toll-Like Receptors / metabolism

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • Cytokines
  • Lectins
  • SIGLEC8 protein, human
  • Toll-Like Receptors
  • Peptide Hydrolases