Journal article
Type I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice
- 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 defense 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 receptor-1 deficient (Ifnar1–/–) mice, to study the role of type I IFN signalling and innate immune responses during SARS-CoV-2 infection. Our data show that type I IFN signalling 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 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 signalling deficiency results in a dysregulated innate immune response to SARS-CoV-2 infection.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 977.1KB, Terms of use)
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- Publisher copy:
- 10.1002/eji.202249913
Authors
- Publisher:
- Wiley
- Journal:
- European Journal of Immunology More from this journal
- Volume:
- 52
- Issue:
- 11
- Pages:
- 1768-1775
- Place of publication:
- Germany
- Publication date:
- 2022-10-07
- Acceptance date:
- 2022-09-13
- DOI:
- EISSN:
-
1521-4141
- ISSN:
-
0014-2980
- Pmid:
-
36106692
- Language:
-
English
- Keywords:
- Pubs id:
-
1279523
- Local pid:
-
pubs:1279523
- Deposit date:
-
2023-02-04
- ARK identifier:
Terms of use
- Copyright holder:
- Ogger et al.
- Copyright date:
- 2022
- Rights 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.
- Licence:
- CC Attribution (CC BY)
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