| 描述信息 |
Type III interferons (IFN) primarily act on epithelial cells and protect mucosa from virus infection, whereas type I IFNs act more systemically. To date, it has been unknown which epithelial subtypes in the upper airways, the primary site for initial infection for most respiratory viruses, primarily rely on type III IFN or type I IFNs for antiviral protection. To address this question, we performed a single-cell transcriptomics analysis to investigate the epithelial IFN response in the upper airways of mice. This work resolved the cellular landscape of the olfactory epithelium and the respiratory epithelium. Interestingly, in respiratory epithelial cells, type I IFN induced more potent antiviral responses than type III IFN, whereas in olfactory epithelial cells, including sustentacular (SUS) and Bowman's gland cells (BGC), type III IFN was dominant and triggered a more robust antiviral response than type I IFN. SUS and BGC, crucial for structural support and maintaining the integrity of olfactory sensory neurons, showed high susceptibility to a mouse-adapted variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, they remained protected against infection when treated with a human type III IFN drug candidate. These findings demonstrate a high degree of cellular heterogeneity and dynamics in interferon-mediated antiviral responses and reveal a specific antiviral role for type III IFN in protecting the olfactory epithelium. |
