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

Abstract

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. Here, using a nasopharyngeal biopsy technique, we investigated longitudinal immune responses in NALT following viral challenge, using SARS-CoV-2 infection as a natural experimental model. In acute infection, infiltrating monocytes 6 formed a subepithelial and peri-follicular shield, recruiting NET-forming neutrophils, whilst tissue macrophages expressed pro-repair molecules during convalescence to promote the restoration of tissue integrity. Germinal centre B cells expressed anti-viral 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 programmes 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.