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

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.

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.

DOI

10.1002/eji.202249913

Type

Journal article

Journal

Eur J Immunol

Publication Date

11/2022

Volume

52

Pages

1768 - 1775

Keywords

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

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