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

Gebremeskel S, Schanin J, Coyle KM, Butuci M, Luu T, Brock EC, Xu AL, Wong AL, Leung J, Korver W, Morin RD, Schleimer RP, Bochner BS, Youngblood BA. Mast Cell and Eosinophil Activation Are Associated With COVID-19 and TLR-Mediated Viral Inflammation: Implications for an Anti-Siglec-8 Antibody. Frontiers in Immunology. 2021;12:12.

Descriptions

Resource type(s)
Article
Keyword
COVID-19
SARS-CoV-2
Toll-like receptor
mast cell
eosinophil
Siglec-8
lirentelimab
viral inflammation
Rights
Attribution 4.0 International

Creator
Gebremeskel, Simon
Schanin, Julia
Coyle, Krysta M.
Butuci, Melina
Luu, Thuy
Brock, Emily C.
Xu, Alan
Wong, Alan
Leung, John
Korver, Wouter
Morin, Ryan D.
Schleimer, Robert P.
Bochner, Bruce S.
Youngblood, Bradford A.
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.
Related URL
Publisher
FRONTIERS MEDIA SA
Date Created
2021-03-10
Original Identifier
(PMID) 33777047
Grants and funding
Allakos, Inc.
DOI
10.3389/fimmu.2021.650331

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