TY - JOUR
T1 - Mast Cell and Eosinophil Activation Are Associated With COVID-19 and TLR-Mediated Viral Inflammation
T2 - Implications for an Anti-Siglec-8 Antibody
AU - Gebremeskel, Simon
AU - Schanin, Julia
AU - Coyle, Krysta M.
AU - Butuci, Melina
AU - Luu, Thuy
AU - Brock, Emily C.
AU - Xu, Alan
AU - Wong, Alan
AU - Leung, John
AU - Korver, Wouter
AU - Morin, Ryan D.
AU - Schleimer, Robert P.
AU - Bochner, Bruce S.
AU - Youngblood, Bradford A.
N1 - Funding Information:
This research was funded by Allakos, Inc.
Publisher Copyright:
© Copyright © 2021 Gebremeskel, Schanin, Coyle, Butuci, Luu, Brock, Xu, Wong, Leung, Korver, Morin, Schleimer, Bochner and Youngblood.
PY - 2021/3/10
Y1 - 2021/3/10
N2 - 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.
AB - 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.
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U2 - 10.3389/fimmu.2021.650331
DO - 10.3389/fimmu.2021.650331
M3 - Article
C2 - 33777047
AN - SCOPUS:85103056306
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 650331
ER -