Submitted to: ARS Immunology Workshop
Publication Type: Abstract only
Publication Acceptance Date: 12/3/2003
Publication Date: 12/3/2003
Citation: HE, H., KOGUT, M.H. STIMULATION OF CHICKEN LEUKOCYTES AND REDUCTION OF SALMONELLA ORGAN INVASION IN NEONATAL CHICKEN BY IMMUNOSTIMULATORY CPG-OLIGODEOXYNUCLEOTIDE. ARS IMMUNOLOGY WORKSHOP. 2003. ABSTRACT P. 25. Interpretive Summary:
Technical Abstract: Unmethylated CpG oligodinucleotide, flanked by particular base contents, are known to stimulate innate immune responses. Immune stimulatory activities of these CpG molecules have been studied mostly in immune cells from mammals, particularly human and mice. Recently, studies have emerged to show similar immune stimulatory activities of CpG oligodinucleotide in other species such as chicken and fish. Our laboratory has recently performed studies on immune stimulatory activities of CpG oligodinucleotide in chicken. Our results show that synthetic oligodeoxynucleotides (ODN) containing CpG motif (CpG-ODN) activated the avian macrophage cell line and induced NO production. The most active CpG-ODN motif for NO induction was GTCGTT. Increasing the number of GTCGTT motif in the CpG-ODN significantly enhanced the stimulatory effect. This CpG-ODN also stimulated IL-1beta gene expression in the macrophage HD11 cells. CpG-ODN stimulated inducible NO synthase (iNOS) to produce NO through a clathrin-dependent endocytosis and subsequent endosomal maturation signaling pathways, involving activation of protein kinase C (PKC), mitogen-activated protein kinases (p38 MAPK and MEK1/2), and transcription factor NF-'B. Moreover, we have discovered that CpG-ODN induces degranulation in chicken heterophils. This heterophil degranulation activity induced by CpG-ODN was absolutely serum-dependent and also receptor mediated. Finally, we evaluated synthetic CpG-ODNs for their in vivo protection against organ invasion by Salmonella enteritidis (SE) in neonatal chickens. Day-old chickens were i.p. injected with synthetic CpG-ODN and then orally challenged with live SE. Organs (liver and spleen) were removed from experimental chickens 24 hours after the challenge and cultured for SE. The results showed a significant reduction of organ invasion by SE (p<0.05) in chickens pretreated with CpG-ODN containing the immunostimulatory GTCGTT motif.