PT - JOURNAL ARTICLE AU - Matthew L. Coates AU - Nathan Richoz AU - Zewen K. Tuong AU - Georgie Bowyer AU - Colin Y.C. Lee AU - John R. Ferdinand AU - Eleanor Gillman AU - Mark McClure AU - Rafael Di Marco Barros AU - Benjamin J Stewart AU - Menna R. Clatworthy TI - Temporal profiling of human lymphoid tissues reveals coordinated defence to viral challenge AID - 10.1101/2023.09.15.558006 DP - 2023 Jan 01 TA - bioRxiv PG - 2023.09.15.558006 4099 - http://biorxiv.org/content/early/2023/09/17/2023.09.15.558006.short 4100 - http://biorxiv.org/content/early/2023/09/17/2023.09.15.558006.full AB - 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, we examined longitudinal immune responses in NALT following viral challenge, using SARS-CoV-2 infection as a natural experimental model. In acute infection, infiltrating monocytes 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 a unique insight into how human nasal adaptive immune responses are generated and sustained in the face of viral challenge.Competing Interest StatementThe authors have declared no competing interest.AMPAntimicrobial peptideB GCGerminal centre B cellB GC DZDark Zone Germinal Centre B cellB GC LZLight Zone Germinal Centre B cellB MemMemory B cellB Mem SwSwitched Memory B cellcDCConventional dendritic cellCTLCytotoxic T cellgdT/γδTGamma-delta T cellILCInnate lymphoid cellMAITMucosal-associated invariant T cellMΦMacrophageMNPMononuclear phagocyteMoDCMonocyte-derived dendritic cellNESNormalised Enrichment ScoreNKNatural killer cellpDCPlasmacytoid dendritic cellTcmT central memory cellTeffT effector cellTemT effector memory cellTfhT follicular helper cellTmemMemory T cellTnNaive T cellTregT regulatory cellTrmT resident memory cellUMAPUniform manifold approximation and projection