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dc.contributor.authorIliev, Dimitar Borisov
dc.contributor.authorLagos, Leidy
dc.contributor.authorThim, Hanna Leena
dc.contributor.authorJørgensen, Sven Martin
dc.contributor.authorKrasnov, Aleksei
dc.contributor.authorJørgensen, Jorunn B
dc.date.accessioned2019-03-29T13:54:10Z
dc.date.available2019-03-29T13:54:10Z
dc.date.issued2019-03-13
dc.description.abstractDue to their ability to present foreign antigens and prime naïve T cells, macrophages, and dendritic cells (DCs) are referred to as professional antigen-presenting cells (APCs). Although activated macrophages may function as APCs, these cells are particularly effective at directly engaging pathogens through phagocytosis, and production of antimicrobial compounds. On the other hand, DCs possess superb antigen-presenting and costimulatory capacity and they are essential for commencement and regulation of adaptive immune responses. In <i>in vitro</i> models, development of mature mammalian DCs from monocytes requires sequential exposure to growth factors (including GM-CSF and IL-4) and proinflammatory stimuli such as toll-like receptor (TLR) ligands. Currently, except for IL-4/13, neither orthologs nor functional analogs of the growth factors which are essential for the differentiation of mammalian DCs (including GM-CSF and FLT3) have been identified in teleosts and data about differentiation of piscine APCs is scant. In the present study, primary salmon mononuclear phagocytes (MPs) stimulated <i>in vitro</i> for 5–7 days with a B-class CpG oligodeoxynucleotides (ODN 2006PS) underwent morphological differentiation and developed “dendritic” morphology, characterized by long, branching pseudopodia. Transcriptional profiling showed that these cells expressed high levels of proinflammatory mediators characteristic for M1 polarized MPs. However, the cells treated with CpGs for 7 days downregulated their surface MHCII molecules as well as their capacity to endocytose ovalbumin and exhibited attenuated allostimulatory activity. This concurred with transcriptional downregulation of costimulatory <i>CD80/86</i> and upregulation of inhibitory <i>CD274 (B7-H1)</i> genes. Despite their exhausted allostimulatory activity, these cells were still responsive to re-stimulation with gardiquimod (a TLR7/8 ligand) and further upregulated a wide array of immune genes including proinflammatory mediators such as <i>intereukin-1 beta</i> and <i>tumor necrosis factor</i>. Overall, the presented data highlight the disparate effects TLR ligands may have on the proinflammatory status of APCs, on one side, and their antigen-presenting/costimulatory functions, on the other. These findings also indicate that despite the poor phylogenetic conservation of the growth factors involved in the differentiation of DCs, some of the processes that orchestrate the development and the differentiation of professional APCs are conserved between teleosts in mammals.en_US
dc.descriptionThe following article, Iliev, D.B., Lagos, L., Thim, H.L., Jørgensen, S.M., Krasnov, A. & Jørgensen, J.B. (2019). CpGs Induce Differentiation of Atlantic Salmon Mononuclear Phagocytes Into Cells With Dendritic Morphology and a Proinflammatory Transcriptional Profile but an Exhausted Allostimulatory Activity. <i>Frontiers in Immunology</i>, can be accessed at <a href=https://doi.org/10.3389/fimmu.2019.00378> https://doi.org/10.3389/fimmu.2019.00378</a>.en_US
dc.identifier.citationIliev, D.B., Lagos, L., Thim, H.L., Jørgensen, S.M., Krasnov, A. & Jørgensen, J.B. (2019). CpGs Induce Differentiation of Atlantic Salmon Mononuclear Phagocytes Into Cells With Dendritic Morphology and a Proinflammatory Transcriptional Profile but an Exhausted Allostimulatory Activity. <i>Frontiers in Immunology</i>. https://doi.org/10.3389/fimmu.2019.00378en_US
dc.identifier.cristinIDFRIDAID 1685059
dc.identifier.doi10.3389/fimmu.2019.00378
dc.identifier.issn1664-3224
dc.identifier.urihttps://hdl.handle.net/10037/15107
dc.language.isoengen_US
dc.publisherFrontiers Mediaen_US
dc.relation.journalFrontiers in Immunology
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/HAVBRUKS/183196/Norway/InNoVacc. Indo-Norway platform for developing candidate vaccines to invertebrate, piscine and avian species//en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMEDBIO/230735/Norway/Exosomes from salmon (Salmo salar) leukocytes - composition, functions, biogenesis and immunodiagnostic potential//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Agriculture and fishery disciplines: 900::Fisheries science: 920en_US
dc.subjectVDP::Landbruks- og Fiskerifag: 900::Fiskerifag: 920en_US
dc.subjectmononuclear phagocytesen_US
dc.subjectantigen-presenting cellsen_US
dc.subjectdendritic cellsen_US
dc.subjectCpG oligodeoxynucleotidesen_US
dc.subjectAtlantic salmonen_US
dc.subjectteleostsen_US
dc.titleCpGs Induce Differentiation of Atlantic Salmon Mononuclear Phagocytes Into Cells With Dendritic Morphology and a Proinflammatory Transcriptional Profile but an Exhausted Allostimulatory Activityen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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