Type‐A CpG oligonucleotides activate exclusively porcine natural interferon‐producing cells to secrete interferon‐α, tumour necrosis factor‐α and interleukin‐12

• Published in: Immunology 2004-05, Vol.112 (1), p.28-37
• Main Authors: Guzylack‐Piriou, Laurence, Balmelli, Carole, McCullough, Kenneth C., Summerfield, Artur
• Format: Article
• Language: English
• Subjects: adjuvants; animal models: studies; Animals; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation - immunology; Cell Survival - immunology; Cells, Cultured; CpG DNA; Cytokines - biosynthesis; Dendritic Cells - immunology; Disease Models, Animal; Fast Track; Immunophenotyping; Interferon-alpha - biosynthesis; Interleukin-12 - biosynthesis; Lipopolysaccharide Receptors - blood; Oligodeoxyribonucleotides - immunology; plasmacytoid dendritic cells; Species Specificity; Swine - immunology; T-Lymphocyte Subsets - immunology; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2004.01856.x

Summary Natural interferon‐producing cells (NIPC), also referred to as immature plasmacytoid dendritic cells (PDC), constitute a small population of leucocytes secreting high levels of type I interferons in response to certain danger signals. Amongst these signals are those from DNA containing unmethylated CpG motifs. The present work demonstrated that the CpG oligonucleotides (CpG‐ODN) 2216, D32 and D19 induce high amounts of interferon‐α (IFN‐α), tumour‐necrosis factor‐α (TNF‐α) and interleukin (IL)‐12 in porcine peripheral blood mononuclear cells (PBMCs). Swine workshop cluster 3 (SWC3)1ow CD4high cells, with high IL‐3‐binding activity, representing NIPC, were the exclusive cytokine‐producing cells responding to the CpG‐ODN. These cells did not express CD6, CD8 or CD45RA. Importantly, monocyte‐derived DC did not respond to CpG‐ODN by secretion of IFN‐α or TNF‐α or by the up‐regulation of costimulatory molecule expression. CpG‐ODN up‐regulated MHC class II and CD80\86 expression on the NIPC, but were unable to promote NIPC survival. Interestingly, certain CpG‐ODN, incapable of inducing NIPC to secrete IFN‐α or up‐regulate MHC class II and CD80\86, did promote NIPC viability. Taken together, the influence of CpG‐ODN on porcine NIPC, monocytes and myeloid DCs relates to that observed with their human equivalents. These results represent an important basis for the application of CpG‐ODN as adjuvants for the formulation of novel vaccines and demonstrate the importance of the pig as an alternative animal model for this approach.