CpG-induced immunomodulation and intracellular bacterial killing in a chicken macrophage cell line

The immunostimulatory properties of synthetic CpG oligodeoxynucleotides (ODNs) have been studied in various mammalian models including humans and mice. However, little was known about effects of CpG ODNs on immune responses of chickens, a common avian species with important economical value in the poultry industry. In the present study, two CpG ODNs, 2006 and 1826, which show immunomodulating properties for humans and mice were tested using a chicken macrophage cell line (HD11). ODN 2006, which has been reported to be an optimal stimulatory sequence for humans, showed strong immunomodulatory effects on HD11 cells, whereas ODN 1826, a CpG sequence with optimal immunostimulatory effects on mice, had weak influences on HD11 cells. ODN 2006 also induced strong IL-6 and nitric oxide secretion by HD11 cells in both dose- and time-dependent manners. Intracellular killing of Salmonella enteritidis (SE) was also increased in ODN 2006-activated HD11 cells. Furthermore, HD11 cells had reduced proliferation and underwent Apoptosis, which is contradictory to the effects of ODN 2006 on human and murine cells. N(G)-monomethyl L-arginine (L-NMMA), an iNOS Inhibitor, inhibited Apoptosis of HD11 cells induced by ODN 2006, suggesting that this effect was likely mediated through an iNOS-dependent pathway. These results indicate that the differences in the responses of chicken HD11 macrophage cells to CpG ODNs compared to those of mammalian macrophages are species-related, and the potential of CpG ODNs as immunomodulators in poultry needs to be further explored.