tetano
Editor, Senior Moderator
Eur J Immunol
. 2022 Sep 15.
doi: 10.1002/eji.202249913. Online ahead of print.
Type I interferon signaling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice
Patricia P Ogger[SUP] 1 [/SUP], Minerva Garcia Martín[SUP] 1 [/SUP], Christina Michalaki[SUP] 1 [/SUP], Jie Zhou[SUP] 2 [/SUP], Jonathan C Brown[SUP] 2 [/SUP], Yue Du[SUP] 3 [/SUP], Kamran M Miah[SUP] 3 [/SUP], Omar Habib[SUP] 3 [/SUP], Stephen C Hyde[SUP] 3 [/SUP], Deborah R Gill[SUP] 3 [/SUP], Wendy S Barclay[SUP] 2 [/SUP], Cecilia Johansson[SUP] 1 [/SUP]
Affiliations
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[SUP]-/-[/SUP] ) 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[SUP]-/-[/SUP] 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[SUP]-/-[/SUP] 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 deficiency results in a dysregulated innate immune response to SARS-CoV-2 infection. This article is protected by copyright. All rights reserved.
Keywords: In vivo; Innate Immune Response/ type I IFN; SARS-CoV-2/ myeloid cells.
. 2022 Sep 15.
doi: 10.1002/eji.202249913. Online ahead of print.
Type I interferon signaling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice
Patricia P Ogger[SUP] 1 [/SUP], Minerva Garcia Martín[SUP] 1 [/SUP], Christina Michalaki[SUP] 1 [/SUP], Jie Zhou[SUP] 2 [/SUP], Jonathan C Brown[SUP] 2 [/SUP], Yue Du[SUP] 3 [/SUP], Kamran M Miah[SUP] 3 [/SUP], Omar Habib[SUP] 3 [/SUP], Stephen C Hyde[SUP] 3 [/SUP], Deborah R Gill[SUP] 3 [/SUP], Wendy S Barclay[SUP] 2 [/SUP], Cecilia Johansson[SUP] 1 [/SUP]
Affiliations
- PMID: 36106692
- DOI: 10.1002/eji.202249913
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[SUP]-/-[/SUP] ) 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[SUP]-/-[/SUP] 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[SUP]-/-[/SUP] 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 deficiency results in a dysregulated innate immune response to SARS-CoV-2 infection. This article is protected by copyright. All rights reserved.
Keywords: In vivo; Innate Immune Response/ type I IFN; SARS-CoV-2/ myeloid cells.