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. 2022 Nov;52(11):1768-1775.
doi: 10.1002/eji.202249913. Epub 2022 Oct 7.

Type I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice

Patricia P Ogger  1 , Minerva Garcia Martín  1 , Christina Michalaki  1 , Jie Zhou  2 , Jonathan C Brown  2 , Yue Du  3 , Kamran M Miah  3 , Omar Habib  3 , Stephen C Hyde  3 , Deborah R Gill  3 , Wendy S Barclay  2 , Cecilia Johansson  1
Affiliations

Type I interferon receptor signalling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice

Patricia P Ogger et al. Eur J Immunol. 2022 Nov.

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.

Keywords: SARS-CoV-2; in vivo; innate immune response; myeloid cells; type I IFN.

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