CpGs Induce Differentiation of Atlantic Salmon Mononuclear Phagocytes Into Cells With Dendritic Morphology and a Proinflammatory Transcriptional Profile but an Exhausted Allostimulatory Activity.

Due 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 in vitro 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 in vitro 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 CD80/86 and upregulation of inhibitory CD274 (B7-H1) 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 intereukin-1 beta and tumor necrosis factor. 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.

Disease resistance is related to inherent swimming performance in Atlantic salmon.

BACKGROUND: Like humans, fish can be classified according to their athletic performance. Sustained exercise training of fish can improve growth and physical capacity, and recent results have documented improved disease resistance in exercised Atlantic salmon. In this study we investigated the effects of inherent swimming performance and exercise training on disease resistance in Atlantic salmon.Atlantic salmon were first classified as either poor or good according to their swimming performance in a screening test and then exercise trained for 10 weeks using one of two constant-velocity or two interval-velocity training regimes for comparison against control trained fish (low speed continuously). Disease resistance was assessed by a viral disease challenge test (infectious pancreatic necrosis) and gene expression analyses of the host response in selected organs. RESULTS: An inherently good swimming performance was associated with improved disease resistance, as good swimmers showed significantly better survival compared to poor swimmers in the viral challenge test. Differences in mortalities between poor and good swimmers were correlated with cardiac mRNA expression of virus responsive genes reflecting the infection status. Although not significant, fish trained at constant-velocity showed a trend towards higher survival than fish trained at either short or long intervals. Finally, only constant training at high intensity had a significant positive effect on fish growth compared to control trained fish. CONCLUSIONS: This is the first evidence suggesting that inherent swimming performance is associated with disease resistance in fish.