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Title: CPG-INDUCED IMMUNOMODULATION AND INTRACELLULAR BACTERIAL KILLING IN A CHICKEN MACROPHAGE CELL LINE

Author
item XIE, HANG - UNIV OF MARYLAND
item RAYBOURNE, RICHARD - FDA
item BABU, UMA - FDA
item Lillehoj, Hyun
item HECKERT, ROBERT - UNIV OF MARYLAND

Submitted to: Developmental and Comparative Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/1/2003
Publication Date: N/A
Citation: N/A

Interpretive Summary: Immunomodulators are substances which can enhance various aspects of host immune response. In mammalian system, it has been well known that certain sequences of bacterial DNA (bDNA) have immune stimulatory effects. Subsequently it was found that the immunostimulatory properties of bDNA are actually due to the highly enriched unmethylated CpG dinucleotide content. In this study, scientists at University of Maryland, Food and Drug Administration and ARS collaborated to discover a novel bacterial DNA sequence which stimulates innate immunity of poultry. Because there is limited information on how these immunomodulators work, application of these immunomodulators in the field has been slow. This study showed that the bacterial DNA such as CpG sequences stimulate macrophages and enhance innate immunity against pathogens such as Salmonella. This finding provides a new strategy for developing therapeutics or more efficient vaccines against intracellular pathogens in poultry.

Technical Abstract: 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 2006 activated HD11 cells. Furthermore, ODN 2006 stimulated HD11 cells had reduced proliferation and underwent apoptosis after CpG stimulation, which is contradictory to its effects on human and murine cells. NG-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 macrophage cells HD11 to CpG ODNs are species-related, and the potential of CpG ODNs as immunomodulators in poultry needs to be further explored.