RT Journal Article
SR Electronic
T1 Temporal profiling of human lymphoid tissues reveals coordinated defence to viral challenge
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.09.15.558006
DO 10.1101/2023.09.15.558006
A1 Matthew L. Coates
A1 Nathan Richoz
A1 Zewen K. Tuong
A1 Georgie Bowyer
A1 Colin Y.C. Lee
A1 John R. Ferdinand
A1 Eleanor Gillman
A1 Mark McClure
A1 Rafael Di Marco Barros
A1 Benjamin J Stewart
A1 Menna R. Clatworthy
YR 2023
UL http://biorxiv.org/content/early/2023/09/17/2023.09.15.558006.abstract
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