Type-A CpG oligonucleotides activate exclusively porcine natural interferon-producing cells to secrete interferon-alpha, tumour necrosis factor-alpha and interleukin-12.
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-alpha (IFN-alpha), tumour-necrosis factor-alpha (TNF-alpha) 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-alpha or TNF-alpha 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-alpha 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.
Guzylack-Piriou
Laurence
L
Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland. laurence.guzylack@ivi.admin.ch
Balmelli
Carole
C
McCullough
Kenneth C
KC
Summerfield
Artur
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000097:blood; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D013045:Species Specificity; D013552:Swine / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C408982:CPG-oligonucleotide; D016207:Cytokines; D016898:Interferon-alpha; D018950:Lipopolysaccharide Receptors; D009838:Oligodeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12