Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant
Year: 2025
Type: article
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 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 explore 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 are involved in the direct initiation of the inflammatory response to adjuvant by monocytes and macrophages (Mon./Mac.) with secretion of interleukin (IL)-1β, but not IL-18, dependent on TLR4 signaling. Innate lymphoid cells, including natural killer cells, are indirectly activated by Mon./Mac.-produced cytokines, signaling downstream to B cells via interferon-γ secretion. Resident LN stromal populations, primed both directly and indirectly by vaccine adjuvant, are instrumental in mediating inflammatory cell recruitment, particularly neutrophils.
Source: Cell Reports
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Bill and Melinda Gates Foundation, National Institute on Handicapped Research, Wellcome Trust, Chan Zuckerberg Initiative, Kennedy Trust for Rheumatology Research, Royal Society, Rosetrees Trust, Deutsche Forschungsgemeinschaft, Medical Research Council, NIHR Oxford Biomedical Research Centre, Janssen Biotech
Awards: G2486546438, Charakterisierung des Wirkmechanismus von VakzinAdjuvantien zur Mechanismusbasierten, „intelligenten“ Impfstoffentwicklung, Investigating the functional basis of shared genetic etiology across autoimmune diseases, Deciphering the impact of human early B cell responses on long-lived antibody responses, Vaccine Formulation Institute (CH) Ltd - To develop a broad portfolio of adjuvants for use in Global Health vaccines, G4601337951, G5897121867, Spatiotemporal control of cytoskeletal remodeling in lymphocytes, G7864623427, Precision genome editing with tandem autologous transplantation as a therapy for multiple severe immune-mediated diseases, (ICF)- IMMPROVE: Immune Memory and Mechanisms of Protection from Vaccines, Spatiotemporal control of cytoskeletal remodeling in lymphocytes, Deciphering the impact of human early B cell responses on long-lived antibody responses, Investigating the functional basis of shared genetic etiology across autoimmune diseases
OpenAlex ID: W4411970439