Type I interferon signaling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice
Author(s)
Type
Journal Article
Abstract
SARS-CoV-2 is a newly emerged coronavirus, causing the global pandemic of respiratory coronavirus disease (COVID-19). The type I interferon (IFN) pathway is of particular importance for anti-viral defence and recent studies identified that type I IFNs drive early inflammatory responses to SARS-CoV-2. Here, we use a mouse model of SARS-CoV-2 infection, facilitating viral entry by intranasal recombinant Adeno-Associated Virus (rAAV) transduction of hACE2 in wildtype (WT) and type I IFN-signalling-deficient (Ifnar1-/- ) mice, to study type I IFN signalling deficiency and innate immune responses during SARS-CoV-2 infection. Our data show that type I IFN signaling is essential for inducing anti-viral effector responses to SARS-CoV-2, control of virus replication and to prevent enhanced disease. Furthermore, hACE2-Ifnar1-/- mice had increased gene expression of the chemokine Cxcl1 and airway infiltration of neutrophils as well as a reduced and delayed production of monocyte-recruiting chemokine CCL2. hACE2-Ifnar1-/- mice showed altered recruitment of inflammatory myeloid cells to the lung upon SARS-CoV-2 infection, with a shift from Ly6C+ to Ly6C- expressing cells. Together, our findings suggest that type I IFN deficiency results in a dysregulated innate immune response to SARS-CoV-2 infection. This article is protected by copyright. All rights reserved.
Date Issued
2022-11
Date Acceptance
2022-09-13
ISSN
0014-2980
Publisher
Wiley
Start Page
1768
End Page
1775
Journal / Book Title
European Journal of Immunology
Volume
52
Issue
11
Copyright Statement
© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor
Rosetrees Trust
Rosetrees Trust
Rosetrees Trust
Rosetrees Trust
Imperial College COVID-19 response fund
UK Research and Innovation
Rosetrees Trust
Identifier
https://onlinelibrary.wiley.com/doi/10.1002/eji.202249913
https://www.ncbi.nlm.nih.gov/pubmed/36106692
Grant Number
M370
M370-F1
M956
M956
BB/V013831/1
A442
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
innate immune response
type I IFN
in vivo
SARS-CoV-2
myeloid cells
TRANSGENE EXPRESSION
SARS-CoV-2
in vivo
innate immune response
myeloid cells
type I IFN
Animals
Mice
COVID-19
Immunity, Innate
Interferon Type I
Pandemics
Receptor, Interferon alpha-beta
SARS-CoV-2
Animals
Mice
Interferon Type I
Receptor, Interferon alpha-beta
Immunity, Innate
Pandemics
COVID-19
SARS-CoV-2
In vivo
Innate Immune Response/ type I IFN
SARS-CoV-2/ myeloid cells
Immunology
1107 Immunology
Publication Status
Published
Coverage Spatial
Germany
Date Publish Online
2022-09-15