PyNTTTTGT and CpG immunostimulatory oligonucleotides: effect on granulocyte/monocyte colony-stimulating factor (GM-CSF) secretion by human CD56+ (NK and NKT) cells

• Published in: PloS one Vol. 10; no. 2; p. e0117484
• Main Authors: Rodriguez, Juan M, Marchicio, José, López, Mariela, Ziblat, Andrea, Elias, Fernanda, Fló, Juan, López, Ricardo A, Horn, David, Zorzopulos, Jorge, Montaner, Alejandro D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23-02-2015; Public Library of Science (PLoS)
• Subjects: CD56 antigen; Colonies; Colony-stimulating factor; CpG islands; Cytokines; Dendritic cells; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Granulocytes; Humans; Immune system; Immunostimulation; Infections; Inhibition; Interference; Interferon; Interferon-alpha - metabolism; Interferon-gamma - metabolism; Interleukin; Interleukin 2; Interleukin-2 - pharmacology; Interleukin-8 - metabolism; Killer Cells, Natural - drug effects; Killer Cells, Natural - metabolism; Leukocytes (granulocytic); Leukocytes (mononuclear); Lymphocytes; Monocytes; Natural Killer T-Cells - drug effects; Natural Killer T-Cells - metabolism; Oligodeoxyribonucleotides - pharmacology; Oligonucleotides; Peripheral blood mononuclear cells; Signal transduction; T cell receptors; TLR9 protein; Toll-like receptors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; γ-Interferon; United States > US; Argentina
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0117484

CD56+ cells have been recognized as being involved in bridging the innate and acquired immune systems. Herein, we assessed the effect of two major classes of immunostimulatory oligonucleotides (ODNs), PyNTTTTGT and CpG, on CD56+ cells. Incubation of human peripheral blood mononuclear cells (hPBMC) with some of these ODNs led to secretion of significant amounts of interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) and granulocyte/monocyte colony-stimulating factor (GM-CSF), but only if interleukin 2 (IL2) was present. IMT504, the prototype of the PyNTTTTGT ODN class, was the most active. GM-CSF secretion was very efficient when non-CpG ODNs with high T content and PyNTTTTGT motifs lacking CpGs were used. On the other hand, CpG ODNs and IFNα inhibited this GM-CSF secretion. Selective cell type removal from hPBMC indicated that CD56+ cells were responsible for GM-CSF secretion and that plasmacytoid dendritic cells (PDCs) regulate this process. In addition, PyNTTTTGT ODNs inhibited the IFNα secretion induced by CpG ODNs in PDCs by interference with the TLR9 signaling pathway. Since IFNα is essential for CD56+ stimulation by CpG ODNs, there is a reciprocal interference of CpG and PyNTTTTGT ODNs when acting on this cell population. This suggests that these synthetic ODNs mimic different natural alarm signals for activation of the immune system.