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STIMULATION OF THE INNATE IMMUNE SYSTEM OF BROILER CHICKS WITH DNA OLIGONUCLEOTIDES CONTAINING CpG MOTIFS (CpG DNA)

Susantha Gomis1, Lorne Babiuk2, Edwin Waters3 , Philip Willson2 , Brenda Allan2 , Rolf Hecker4, and Andrew Potter2.

1Dept. of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5B4, Canada.

2 Vaccine and Infectious Disease Organization, 120 Veterinary Road, Saskatoon, SK. Canada S7N 5E3.

3 Prairie Diagnostic Services, 52, Campus Dr. Saskatoon, SK. S7N 5B4.

4 Qiagen GmbH, Hilden, Germany

Identification of events and signals that can boost immune responses to pathogens has been an active area of investigation for over 30 years. These studies have led to the discovery of various immunomodulators as well as the cytokine pathways that direct the immune response and allow cellular communication. Oligonucleotides containing CpG motifs caused proliferation of lymphocytes, up-regulation of MHC Class II, IgG-producing cells and other non-specific responses. These studies clearly indicate that CpG has immunomodulatory effects. Furthermore, these studies have led to the evolution of the "danger" hypothesis that cells of the immune system can rapidly respond to bacterial invaders. This allows the host to clear the bacterial infection even before specific immune responses are developed. In addition, CpG directly can activate monocytes/macrophages or dendritic cells to secrete interferon, IL-6, IL-12, GMCSF, chemokines, and TNF-α. Similarly, CpG either directly or through the cytokines produced by antigen-presenting cells, stimulate NK cells to produce IFN-γ as well as increase their killing activity.

Synthetic bacterial DNA oligonucleotides containing CpG motifs (CpG-DNA) have been shown to be effective immunoprotective agents in murine models. The objective of this study was to investigate the effect of CpG-DNA in a day old broiler model of E. coli septicemia. The control group of birds that received no CpG-DNA had a survival rate of 10%. In contrast, groups that received CpG-DNA by intramuscular injection had a significantly higher survival rate of 90% (p<0.01). This study demonstrates that CpG-DNA have immunoprotective effects against E. coli septicemia in broiler chicks. This is the first time that CpG-ODN has been demonstrated to have an immunoprotective effect against an extracellular bacterial infection in broiler chicks.

Western Meeting of Poultry Clinicians and Pathologists – Sep. 30, 2003

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