Western
Meeting of Poultry
Clinicians and Pathologists
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Clinicians and Pathologists
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Stimulation of the Immune System of Broilers Against Cellulitis / Collibacillosis Gomis Susantha1,2, Babiuk Lorne1, Thrush, Tannis1, Waters Edwin2, Allan Brenda1 Hecker Rolf3, and Andrew Potter1. 1 Veterinary Infectious Disease Organization, 120 Veterinary Road, Saskatoon, SK. S7N 5E3. 2 Dept. of Veterinary Pathology, WCVM, University of Saskatchewan, 52, Campus Dr. Saskatoon, SK. S7n 5b4. 3 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. As part of these studies, investigations into the active component of BCG used in cancer treatment demonstrated that the immune modulation activity resided in a DNA-rich fraction. From these studies, it has been concluded that oligonucleotides (ODN) containing a 6 base motif centered on a CpG dinucleotide were responsible for these activities. In parallel studies, others discovered that ODN’s caused proliferation of lymphocytes, up-regulation of MHC Class II, increased the number of IgG-producing cells, etc. These complementary studies clearly indicated that DNA had immunomodulatory effects. These studies have led to the evolution of the “danger” hypothesis where it is proposed 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. These discoveries have clearly altered our appreciation of the interactions between the innate (non-specific) and adaptive (specific) immune responses. Thus, CpG motifs can stimulate a cytokine cascade that directs the immune response. That these CpG motifs favor the Th1-dominated cytokine pathway explains the predominance of Th1-like responses following DNA immunization and the switch to Th1-like responses if it is used as an adjuvant with subunit or conventional vaccines. In addition, CpG directly can activate monocytes/macrophages or dendritic cells (antigen-presenting 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. These synthetic bacterial DNA (CpG-ODN) have been shown to be effective immunoprotective agents in murine models against a variety of intracellular bacterial, protozoan and viral agents. Until now, the use of CpG-ODN as an immunostimulant against bacterial infections in chickens has not been reported. The objective of this study was to investigate the effect of CpG-ODN against cellulitis / colibacillosis in broilers using a well-established model. Broilers chicks were raised and maintained in an isolation facility. At 22 days of age, birds received CpG-ODN either by subcutaneous or intramuscular route at doses of 10 or 50 mg/bird. At day 25, a virulent isolate of E. coli was applied on a scratch site on the caudal abdominal region. Birds were examined for 10 days post E. coli challenge and pathological and bacteriological assessments were conducted on all dead or euthanized birds. The control group of birds that received no CpG-ODN had a survival rate of 15%. In contrast, groups that received CpG-ODN by subcutaneous or intramuscular injection had significantly higher survival rates. The size of the cellulitis lesion was significantly smaller in groups that received CpG-ODN by subcutaneous route (p<0.01). This study demonstrated that CpG-ODN has both localized and systemic immunoprotective effects in broilers. |
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