Nasal immunity in respiratory viral infection, transmission, and protection

The nasal mucosa plays key roles in protecting against airborne pathogens as the major barrier to the airway. Catalyzed by the COVID-19 pandemic, recent studies focusing on nasal immunity have begun to elucidate how epithelial and immune cells work in concert to fight viral infection, reduce spread to the lower airways, and limit onward transmission. Technologies such as single-cell RNA sequencing and air-liquid interface models are enabling high-resolution views of the cell states and responses that dictate infection resolution and memory formation. Here, we review our current understanding of the cells of the nasal mucosa at homeostasis and their responses during and following viral infection in mice and humans. We discuss emerging correlates of protection before and after exposure, noting the differences between infection and intramuscular vaccination. Finally, we examine novel intranasal vaccination strategies and propose approaches to program tissue-scale memory into the nose to prevent disease and viral spread.