Primary nasal viral infection rewires the tissue-scale memory response

Area of Science:

• Immunology
• Respiratory Virology
• Single-cell genomics

Background:

• The nasal mucosa is a key site for respiratory viral infections.
• Understanding coordinated immune cell responses in the nasal mucosa is crucial for developing effective vaccines and therapeutics.
• The impact of primary infection on memory responses to secondary challenge needs further clarification.

Approach:

• Generated a single-cell RNA-sequencing atlas of the murine nasal mucosa across primary and secondary influenza infection.
• Analyzed cell type, subset, and state composition changes over time in distinct nasal regions.
• Utilized proportionality analysis, cell-cell communication inference, and in situ microscopy for validation.

Key Points:

• Primary influenza infection induced stepwise immune cell changes, including neutrophils, epithelial cells, monocytes, NK cells, macrophages, and T cells.
• Unique Krt13+ nasal immune-interacting floor epithelial (KNIIFE) cells emerged post-infection, alongside tissue-resident memory T (T RM)-like cells and plasmablasts.
• CXCL16-CXCR6 signaling was identified between myeloid-derived macrophages and CD8 T cells, and between KNIIFE cells and T RM cells.

Conclusions:

• The study provides a comprehensive atlas of nasal mucosal immune responses to influenza.
• Coordinated myeloid and lymphoid cell memory responses are critical for efficient protection upon secondary viral challenge.
• These findings inform the design of nasal-targeting vaccines and therapeutics for respiratory viruses.