title: Innate immune pathways in afferent lymph following vaccination with poly(I:C)-containing liposomes.
abstract: Many modern vaccines use defined adjuvants to stimulate the innate immune system and shape the adaptive immune response. The exact nature of these innate signals and whether immune differentiation can originate within the periphery is not known. Here we used an ovine lymphatic cannulation model to characterise the cellular and transcriptomic profile of the afferent lymph following injection of a liposomal vaccine formulation incorporating diphtheria toxoid and the innate stimulator poly(I:C) over a 78-h period. The response to this vaccine featured an early activation of broad pro-inflammatory pathways (e.g. TLR signalling and inflammasome pathways) and the transient recruitment of granulocytes into the lymph. At 24 h a more monocytic cellular profile arose coinciding with a transition to a specific antiviral response characterised by the up-regulation of genes associated with the receptors typical for the viral mimic, poly(I:C) (e.g. TLR3, RIG-I and MDA5). At the latest time points the up-regulation of IL-17A and IL-17F suggested that Th17 cells may participate in the earliest adaptive response to this vaccine. These data provide the most comprehensive picture of the cellular and molecular mechanisms that link the periphery to the draining lymph node following vaccination, and indicate that the immune response is capable of specialising within the periphery.
authors.affiliation: Biotechnology Research Laboratories, School of Biomedical Sciences, Monash University, VIC, Australia.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Burke
authors.affiliation: Biotechnology Research Laboratories, School of Biomedical Sciences, Monash University, VIC, Australia michael.deveer@monash.edu.
authors.forename: Michael de
authors.initials: Md
authors.lastname: Veer
authors.affiliation: Biotechnology Research Laboratories, School of Biomedical Sciences, Monash University, VIC, Australia.
authors.forename: Jill
authors.initials: J
authors.lastname: Pleasance
authors.affiliation: Biotechnology Research Laboratories, School of Biomedical Sciences, Monash University, VIC, Australia.
authors.forename: Melanie
authors.initials: M
authors.lastname: Neeland
authors.affiliation: Veterinary Medicine Research and Development, Zoetis, Parkville, VIC, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Elhay
authors.affiliation: Victorian Bioinformatics Consortium, Monash University, VIC, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Harrison
authors.affiliation: Biotechnology Research Laboratories, School of Biomedical Sciences, Monash University, VIC, Australia Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, VIC, Australia.
authors.forename: Els
authors.initials: E
authors.lastname: Meeusen
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004168:Diphtheria Toxoid / Q000494:pharmacology; D006098:Granulocytes / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D058847:Inflammasomes / Q000187:drug effects; D020381:Interleukin-17 / Q000096:biosynthesis; D008081:Liposomes; D008196:Lymph / Q000276:immunology*; D011070:Poly I-C / Q000276:immunology* / Q000494:pharmacology*; D012756:Sheep; D058504:Th17 Cells; D051193:Toll-Like Receptors; D015854:Up-Regulation / Q000187:drug effects; D014611:Vaccination
chemical_list: D000998:Antiviral Agents; D004168:Diphtheria Toxoid; D058847:Inflammasomes; D020381:Interleukin-17; D008081:Liposomes; D051193:Toll-Like Receptors; D011070:Poly I-C
keywords: Innate signalling; granulocytes; lymphatics; ovine