Interferon-lambda uniquely promotes CD8 T cell immunity against SARS-CoV-2 relative to type I interferon
Optimization of protective immune responses against SARS-CoV-2 remains an urgent worldwide priority. In this regard, type III interferon (Interferon-lambda, IFNl) restricts SARS-CoV-2 infection in vitro and treatment with IFNl limits infection, inflammation, and pathogenesis in murine models. Further, IFNl has been developed for clinical use to prevent illness during COVID-19. However, whether endogenous IFNl signaling has an impact on SARS-CoV-2 antiviral immunity and long-term immune protection in vivo is unknown. In this study, we identified a requirement for IFNl signaling in promoting viral clearance and protective immune programming in SARS-CoV-2 infection of mice. Both IFN and IFN-stimulated gene (ISG) expression in the lungs was independent of IFNl signaling. Instead, IFNl promoted generation of protective CD8 T cell responses against SARS-CoV-2 by facilitating accumulation of CD103+ DC in lung-draining lymph nodes. Conversely, CD8 T cell immunity to SARS-CoV-2 is independent of type I IFN signaling, revealing a unique dependence on IFNl. Overall, these studies demonstrate that IFNl is critical for protective innate and adaptive immunity upon infection with SARS-CoV-2, and suggest that IFNl serves as an immune adjuvant to support CD8 T cell immunity. Overall design: C57BL6/J WT or Ifnlr1-/- mice were infected with 10^5 TCID50 of SARS-CoV-2 MA10. Lungs were harvested from naïve mice, or on days 2 or 5 following infection. RNA was extracted from whole lung homogenates and RNAseq and gene expression analysis was performed