tetano
Editor, Senior Moderator
JCI Insight
. 2024 May 21;9(13):e171830.
doi: 10.1172/jci.insight.171830. IFN-λ uniquely promotes CD8 T cell immunity against SARS-CoV-2 relative to type I IFN
Abigail D Solstad[SUP] 1 2 [/SUP], Parker J Denz[SUP] 1 2 [/SUP], Adam D Kenney[SUP] 1 2 [/SUP], Najmus S Mahfooz[SUP] 1 2 [/SUP], Samuel Speaks[SUP] 1 [/SUP], Qiaoke Gong[SUP] 1 [/SUP], Richard T Robinson[SUP] 1 2 [/SUP], Matthew E Long[SUP] 3 4 [/SUP], Adriana Forero[SUP] 1 2 3 [/SUP], Jacob S Yount[SUP] 1 2 [/SUP], Emily A Hemann[SUP] 1 2 3 [/SUP]
Affiliations
Optimization of protective immune responses against SARS-CoV-2 remains an urgent worldwide priority. In this regard, type III IFN (IFN-λ) restricts SARS-CoV-2 infection in vitro, and treatment with IFN-λ limits infection, inflammation, and pathogenesis in murine models. Furthermore, IFN-λ has been developed for clinical use to limit COVID-19 severity. However, whether endogenous IFN-λ signaling has an effect on SARS-CoV-2 antiviral immunity and long-term immune protection in vivo is unknown. In this study, we identified a requirement for IFN-λ signaling in promoting viral clearance and protective immune programming in SARS-CoV-2 infection of mice. Expression of both IFN and IFN-stimulated gene (ISG) in the lungs were minimally affected by the absence of IFN-λ signaling and correlated with transient increases in viral titers. We found that IFN-λ supported the generation of protective CD8 T cell responses against SARS-CoV-2 by facilitating accumulation of CD103+ DC in lung draining lymph nodes (dLN). IFN-λ signaling specifically in DCs promoted the upregulation of costimulatory molecules and the proliferation of CD8 T cells. Intriguingly, antigen-specific CD8 T cell immunity to SARS-CoV-2 was independent of type I IFN signaling, revealing a nonredundant function of IFN-λ. Overall, these studies demonstrate a critical role for IFN-λ in protective innate and adaptive immunity upon infection with SARS-CoV-2 and suggest that IFN-λ serves as an immune adjuvant to support CD8 T cell immunity.
Keywords: Immunology; Infectious disease; Innate immunity; Mouse models; T cells.
. 2024 May 21;9(13):e171830.
doi: 10.1172/jci.insight.171830. IFN-λ uniquely promotes CD8 T cell immunity against SARS-CoV-2 relative to type I IFN
Abigail D Solstad[SUP] 1 2 [/SUP], Parker J Denz[SUP] 1 2 [/SUP], Adam D Kenney[SUP] 1 2 [/SUP], Najmus S Mahfooz[SUP] 1 2 [/SUP], Samuel Speaks[SUP] 1 [/SUP], Qiaoke Gong[SUP] 1 [/SUP], Richard T Robinson[SUP] 1 2 [/SUP], Matthew E Long[SUP] 3 4 [/SUP], Adriana Forero[SUP] 1 2 3 [/SUP], Jacob S Yount[SUP] 1 2 [/SUP], Emily A Hemann[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 38973611
- DOI: 10.1172/jci.insight.171830
Optimization of protective immune responses against SARS-CoV-2 remains an urgent worldwide priority. In this regard, type III IFN (IFN-λ) restricts SARS-CoV-2 infection in vitro, and treatment with IFN-λ limits infection, inflammation, and pathogenesis in murine models. Furthermore, IFN-λ has been developed for clinical use to limit COVID-19 severity. However, whether endogenous IFN-λ signaling has an effect on SARS-CoV-2 antiviral immunity and long-term immune protection in vivo is unknown. In this study, we identified a requirement for IFN-λ signaling in promoting viral clearance and protective immune programming in SARS-CoV-2 infection of mice. Expression of both IFN and IFN-stimulated gene (ISG) in the lungs were minimally affected by the absence of IFN-λ signaling and correlated with transient increases in viral titers. We found that IFN-λ supported the generation of protective CD8 T cell responses against SARS-CoV-2 by facilitating accumulation of CD103+ DC in lung draining lymph nodes (dLN). IFN-λ signaling specifically in DCs promoted the upregulation of costimulatory molecules and the proliferation of CD8 T cells. Intriguingly, antigen-specific CD8 T cell immunity to SARS-CoV-2 was independent of type I IFN signaling, revealing a nonredundant function of IFN-λ. Overall, these studies demonstrate a critical role for IFN-λ in protective innate and adaptive immunity upon infection with SARS-CoV-2 and suggest that IFN-λ serves as an immune adjuvant to support CD8 T cell immunity.
Keywords: Immunology; Infectious disease; Innate immunity; Mouse models; T cells.