Submitted to: Developmental and Comparative Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 11/15/2002
Publication Date: 4/21/2003
Citation: HE,H. ., CRIPPEN,T.L., FARNELL,M.B., KOGUT,M.H., IDENTIFICATION OF CPG OLIGODEOXYNUCLEOTIDE MOTIFS THAT STIMULATE NITRIC OXIDE AND CYTOKINE PRODUCTION IN AVIAN MACROPHAGE AND PERIPHERAL BLOOD MONONUCLEAR CELLS, DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY, : 27 (2003) 621-627. Interpretive Summary: DNA is the genetic blueprint of life and occurs in all cells. DNA found in bacteria contains a unique element, called CpG-DNA. A white blood cell found in chickens called the macrophage can produce chemicals that can kill bacteria. These bacteria-killing chemicals help chickens fight bacterial infections and therefore stay healthy. We have performed experiments to see if chicken macrophages produce bacteria-killing chemicals when they are exposed to the CpG-DNA. We found that the chicken macrophage can make bacteria-killing chemicals after contact with CpG-DNA. We also found that the chicken macrophage can produce different types and amounts of bacteria-killing chemicals depending upon the type of CpG-DNA contacted. This information is important to the pharmaceutical and poultry industries in the United States because it may offer a new method of producing healthy chickens and reduce the need for antibiotics.
Technical Abstract: Unmethylated CpG dinucleotides in particular base contents that are relatively abundant in bacterial DNA are known to stimulate innate immune responses including immune cell proliferation and cytokine secretion in mammals. In this study, >20 synthetic CpG oligodeoxynucleotides (CpG-ODN) were screened for their ability to stimulate nitric oxide (NO), IL-1beta, and IFN-gamma production using chicken macrophage cell HD-11 and peripheral blood mononuclear cells. Our results showed that synthetic oligodeoxynucleotides containing CpG motif were able to activate the avian macrophage cells and induce NO production. The optimal CpG-ODN motif for NO induction was GTCGTT. Increase of the number of GTCGTT motifs in the CpG-ODN significantly enhanced the stimulatory effect. Deviation of one or two flanking bases on the CpG dinucleotide reduced or diminished the stimulatory activity. We also found that CpG-ODN differentially stimulated expression of cytokine genes. The optimal CpG motif for NO induction was also a strong stimulant for the IL-1beta gene expression in the macrophage HD-11 cells, whereas different CpG motifs were found to induce the IFN-gamma gene expression in PMNC.