Type I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Wiley
2022
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| _version_ | 1797109567129124864 |
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| author | Ogger, PP Garcia Martín, M Michalaki, C Zhou, J Brown, JC Du, Y Miah, KM Habib, O Hyde, SC Gill, DR Barclay, WS Johansson, C |
| author_facet | Ogger, PP Garcia Martín, M Michalaki, C Zhou, J Brown, JC Du, Y Miah, KM Habib, O Hyde, SC Gill, DR Barclay, WS Johansson, C |
| author_sort | Ogger, PP |
| collection | OXFORD |
| description | 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 <i>hACE2</i> in wildtype (WT) and type I IFN receptor-1 deficient (<i>Ifnar1<sup>–/–</sup></i>) 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, <i>hACE2-Ifnar1<sup>–/–</sup></i> mice had increased gene expression of the chemokine <i>Cxcl1</i> and airway infiltration of neutrophils as well as reduced and delayed production of monocyte-recruiting chemokine CCL2. <i>hACE2-Ifnar1<sup>–/–</sup></i> mice showed altered recruitment of inflammatory myeloid cells to the lung upon SARS-CoV-2 infection, with a shift from Ly6C<sup>+</sup> to Ly6C<sup>–</sup> expressing cells. Together, our findings suggest that type I IFN signalling deficiency results in a dysregulated innate immune response to SARS-CoV-2 infection. |
| first_indexed | 2024-03-07T07:43:32Z |
| format | Journal article |
| id | oxford-uuid:281859ec-39fe-41f2-8956-304022aee0ea |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:43:32Z |
| publishDate | 2022 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:281859ec-39fe-41f2-8956-304022aee0ea2023-05-23T15:46:17ZType I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in miceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:281859ec-39fe-41f2-8956-304022aee0eaEnglishSymplectic ElementsWiley2022Ogger, PPGarcia Martín, MMichalaki, CZhou, JBrown, JCDu, YMiah, KMHabib, OHyde, SCGill, DRBarclay, WSJohansson, CSARS-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 <i>hACE2</i> in wildtype (WT) and type I IFN receptor-1 deficient (<i>Ifnar1<sup>–/–</sup></i>) 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, <i>hACE2-Ifnar1<sup>–/–</sup></i> mice had increased gene expression of the chemokine <i>Cxcl1</i> and airway infiltration of neutrophils as well as reduced and delayed production of monocyte-recruiting chemokine CCL2. <i>hACE2-Ifnar1<sup>–/–</sup></i> mice showed altered recruitment of inflammatory myeloid cells to the lung upon SARS-CoV-2 infection, with a shift from Ly6C<sup>+</sup> to Ly6C<sup>–</sup> expressing cells. Together, our findings suggest that type I IFN signalling deficiency results in a dysregulated innate immune response to SARS-CoV-2 infection. |
| spellingShingle | Ogger, PP Garcia Martín, M Michalaki, C Zhou, J Brown, JC Du, Y Miah, KM Habib, O Hyde, SC Gill, DR Barclay, WS Johansson, C Type I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice |
| title | Type I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice |
| title_full | Type I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice |
| title_fullStr | Type I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice |
| title_full_unstemmed | Type I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice |
| title_short | Type I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice |
| title_sort | type i interferon receptor signalling deficiency results in dysregulated innate immune responses to sars cov 2 in mice |
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