Temporal profiling of human lymphoid tissues reveals coordinated defense against viral challenge.

Adaptive immunity is generated in lymphoid organs, but how these structures defend themselves during infection in humans is unknown. The nasal epithelium is a major site of viral entry, with adenoid nasal-associated lymphoid tissue (NALT) generating early adaptive responses. In the present study, using a nasopharyngeal biopsy technique, we investigated longitudinal immune responses in NALT after a viral challenge, using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as a natural experimental model. In acute infection, infiltrating monocytes formed a subepithelial and perifollicular shield, recruiting neutrophil extracellular trap-forming neutrophils, whereas tissue macrophages expressed pro-repair molecules during convalescence to promote the restoration of tissue integrity. Germinal center B cells expressed antiviral transcripts that inversely correlated with fate-defining transcription factors. Among T cells, tissue-resident memory CD8 T cells alone showed clonal expansion and maintained cytotoxic transcriptional programs into convalescence. Together, our study provides unique insights into how human nasal adaptive immune responses are generated and sustained in the face of viral challenge.