CpG-Independent Synergistic Induction of β-Chemokines and a Dendritic Cell Phenotype by Orthophosphorothioate Oligodeoxynucleotides and Granulocyte-Macrophage Colony-Stimulating Factor in Elutriated Human Primary Monocytes

This study investigates how orthophosphorothioate oligodeoxynucleotides (PS-ODN) and granulocyte-macrophage colony-stimulating factor (GM-CSF) work together to enhance immune responses in human primary monocytes. The researchers found that combining these two agents synergistically induces high levels of β-chemokines (CCL3/MIP-1α and CCL4/MIP-1β) and promotes the differentiation of monocytes into dendritic cells (DCs), which are key players in immune responses.

Key findings:

1. Synergistic Chemokine Production: PS-ODN and GM-CSF together significantly increase the production of CCL3 and CCL4, which attract Th1 cells and are crucial for controlling infections like HIV-1.

   
   

2. Dendritic Cell Differentiation: The combination also induces the expression of dendritic cell markers such as CD83, CD86, CD40, and HLA-DR, while reducing CD14 expression, suggesting a differentiation of monocytes into a DC-like phenotype.

   
   

3. CpG-Independent Effect: This effect occurs regardless of the presence of CpG motifs in the ODN, indicating a novel mechanism where PS-ODN (non-CpG) can still potentiate GM-CSF-induced immune activation.

   
   

4. Phosphorothioate Backbone Dependence: The study found that the ability of PS-ODN to stimulate chemokine production is dependent on the phosphorothioate backbone, which is resistant to degradation and aids in immune signaling.

   
   

The findings suggest that the combination of PS-ODN and GM-CSF may be a potent tool for generating dendritic cells ex vivo for immunotherapy and as a potential adjuvant in vaccines against infectious diseases, including HIV-1.

https://journals.aai.org/jimmunol/article/174/10/6113/36616/CpG-Independent-Synergistic-Induction-of