Phosphorothioated CpG Oligonucleotide induced hemopoietic changes in mice

Bacterial DNA and the synthetic CpG-oligodeoxynucleotides (ODNs) derived thereof have attracted attention because they activate cells of the adaptive immune system (lymphocytes) and the innate immune system (macrophages). They induce a Th1 biased immune response upon activation of the immune cells. In this paper we addressed whether unmethylated phosphorothioated CpG ODN (for example 1826 CpG-ODNs) affected hemopoiesis. We observed an overall Th1 dominant response upon in-vitro stimulation of naïve splenocytes with 1826-ODN. Immunizing mice with immunostimulatory CpG motifs led to transient splenomegaly, with a maximum increase of spleen weight at 4 weeks post immunization. Thereafter the splenomegaly regressed. The induction of splenomegaly by CpG-ODNs was dose-dependent with the maximum spleen weights recorded at the 250 μg immunizing dosage of 1826-ODN. In addition, the splenomegaly was also associated with dose dependent extramedullary hemopoiesis and reactive follicular hyperplasia in the spleens and lymph nodes, which could be of therapeutic relevance particularly in patients with life threatening chronic and persistent infectious diseases like visceral leishmaniasis and HIV infection.