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Ex vivo Model of Functioning Human Lymph Node Reveals Role for Innate Lymphocytes and Stroma in Response to Vaccine Adjuvant

ABSTRACT: Immunological processes that underpin human immune responses to therapeutics and vaccine components, such as vaccine adjuvants, remain poorly defined due to a paucity of models that can faithfully recapitulate immune activation in lymphoid tissues. We describe precision-cut human lymph node (LN) slices as a functioning, architecturally-preserved, full-organ cross-sectional model system. Using single cell transcriptomics and multiplexed imaging we explored early inflammatory response to a potent, clinically-relevant liposomal vaccine adjuvant containing a TLR4-agonist and QS-21 saponin. Both TLR4 and NLRP3 inflammasome activation were involved in the direct initiation of the inflammatory response to adjuvant by monocytes and macrophages (Mon./Mac.) with secretion of IL-1b, but not IL-18, found to be TLR4-dependent. Innate lymphoid cells, including NK cells, were indirectly activated by Mon./Mac.-produced cytokines, signalling downstream to B cells via IFNg secretion. Resident LN stromal populations were primed both directly and indirectly by vaccine adjuvant and were instrumental in mediating inflammatory cell recruitment, particularly neutrophils.

ORGANISM(S): Homo sapiens

PROVIDER: GSE294959 | GEO | 2025/07/01

REPOSITORIES: GEO

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