Single-cell transcriptomics reveals a compartmentalized antiviral interferon response in the nasal epithelium of mice

Abstract

SARS-CoV-2 infects SUS and BGC in the olfactory epithelium, causing an impairment of structural support and integrity of olfactory sensory neurons that can result in severe olfactory dysfunctions. We observed an unexpected compartmentalization of the IFN-mediated transcriptional response within the airway epithelium, and we found that olfactory epithelial cells preferentially respond to type III IFN, which resulted in robust antiviral protection of SUS and BGC. Given the proximity of the olfactory epithelium to the central nervous system, we hypothesize that evolution favored a type III IFN-biased antiviral immune response in this tissue to limit inflammatory responses in the brain. Cell type-specific antiviral responses in the upper airways, triggered by the different types of IFNs, should be investigated in more detail and carefully taken into consideration during the development of IFN-based antivirals for clinical use.