CpG oligodeoxynucleotide and double-stranded RNA synergize to enhance nitric oxide production and mRNA expression of inducible nitric oxide synthase,pro-inflammatory cytokines and chemokines in chicken monocytes
Free accessOtherFirst published online April, 2011
CpG oligodeoxynucleotide and double-stranded RNA synergize to enhance nitric oxide production and mRNA expression of inducible nitric oxide synthase,pro-inflammatory cytokines and chemokines in chicken monocytes
Toll-like receptors (TLRs) recognize microbial components and initiate the innate immune responses that control microbial infections. The interaction between ligands of TLR3 and TLR9, poly I:C (an analog of viral double-stranded RNA) and CpG-ODN (a CpG-motif containing oligodeoxydinucleotide) on the inflammatory immune responses, including the production of nitric oxide (NO) and the expression of inducible NO synthase (iNOS), pro-inflammatory cytokines interleukin (IL)-1β and IL-6, and chemokines IL-8 and macrophage inflammatory protein (MIP)-1β, were investigated in chicken monocytes. The NO production was significantly higher when stimulated with a combination of CpG-ODN and poly I:C than with either CpG-ODN or poly I:C alone. Similarly, a significant synergistic effect by CpG-ODN and poly I:C was observed in the up-regulation of iNOS and IL-8 mRNA after 2 h and persisted up to 24 h. Although the combinatory treatment of CpG-ODN and poly I:C enhanced the expression of IL-1β, IL-6, and MIP-1β(3 after 2 h stimulation, the synergism in the up-regulation of IL-1β and IL-6 mRNA was observed after 8-h and 24-h stimulation, respectively, whereas there was no synergistic effect on MIP-1β. Our results demonstrate that CpG-ODN synergizes with poly I:C to induce pro-inflammatory immune response in chicken monocytes.
O’Neill LAHow Toll-like receptors signal: what we know and what we don’t know. Curr Opin Immunol2006; 18: 3-9.
4.
Kaiser P.The avian immune genome - a glass half-full or half-empty?Cytogenet Genome Res2007; 117: 221-230.
5.
Temperley ND , Berlin S., Paton IR et al. Evolution of the chicken Toll-like receptor gene family: a story of gene gain and gene loss. BMC Genomics2008; 9: 62.
6.
Farnell MB, Crippen TL, He H. et al. Oxidative burst mediated by Toll-like receptors (TLR) and CD14 on avian heterophils stimulated with bacterial Toll agonists. Dev Comp Immunol2003; 27: 423-429.
7.
He H., Crippen TL, Farnell MB et al. Identification of CpG oligodeoxynucleotide motifs that stimulate nitric oxide and cytokine production in avian macrophage and peripheral blood mononuclear cells. Dev Comp Immunol2003; 27: 621-627.
8.
He H., Lowry VK, Ferro PJ et al. CpG-oligodeoxynucleotidestimulated chicken heterophil degranulation is serum cofactor and cell surface receptor dependent. Dev Comp Immunol2005; 29: 255-264.
9.
He H., Lowry VK, Swaggerty CL et al. In vitro activation of chicken leukocytes and in vivo protection against Salmonella enteritidis organ invasion and peritoneal S. enteritidis infection-induced mortality in neonatal chickens by immunostimulatory CpG oligodeoxynucleotide. FEMS Immunol Med Microbiol2005; 43: 81-89.
10.
He H., Genovese KJ, Nisbet DJ et al. Synergy of CpG oligodeoxynucleotide and double-stranded RNA (poly I:C) on nitric oxide induction in chicken peripheral blood monocytes. Mol Immunol2007; 44: 3234-3242.
11.
He H., Genovese KJ, Swaggerty CL et al. In vivo priming heterophil innate immune functions and increasing resistance to Salmonella enteritidis infection in neonatal chickens by immune stimulatory CpG oligodeoxynucleotides. Vet Immunol Immunopathol2007; 117: 275-283.
12.
Higuchi M., Matsuo A., Shingai M. et al. Combinational recognition of bacterial lipoproteins and peptidoglycan by chicken Toll-like receptor 2 subfamily. Dev Comp Immunol2008; 32: 147-155.
13.
Iqbal M., Philbin VJ, Withanage GS et al. Identification and functional characterization of chicken Toll-like receptor 5 reveals a fundamental role in the biology of infection with Salmonella enterica serovar typhimurium. Infect Immun2005; 73: 2344-2350.
14.
Jenkins KA, Lowenthal JW, Kimpton W. et al. The in vitro and in ovo responses of chickens to TLR9 subfamily ligands. Dev Comp Immunol2009; 33: 660-667.
15.
Kogut MH, Iqbal M., He H. et al. Expression and function of Toll-like receptors in chicken heterophils . Dev Comp Immunol2005; 29: 791-807.
16.
Kogut MH, Swaggerty C., He H. et al. Toll-like receptor agonists stimulate differential functional activation and cytokine and chemokine gene expression in heterophils isolated from chickens with differential innate responses. Microb Infect2006; 8: 1866-1874.
17.
Keestra AM, de Zoete MR, van Aubel RA et al. The central leucine-rich repeat region of chicken TLR16 dictates unique ligand specificity and species-specific interaction with TLR2. J Immunol2007; 178: 7110-7119.
18.
Keestra AM, de Zoete MR, van Aubel RA et al. Functional characterization of chicken TLR5 reveals species-specific recognition of flagellin. Mol Immunol2008 ; 45: 1298-1307.
19.
Karpala AJ, Lowenthal JW, Bean AGActivation of the TLR3 pathway regulates IFNbeta production in chickens. Dev Comp Immunol2008; 32: 435-444.
20.
Philbin VJ, Iqbal M., Boyd Y. et al. Identification and characterization of a functional, alternatively spliced Toll-like receptor 7 (TLR7) and genomic disruption of TLR8 in chickens . Immunology2005; 114: 507-521.
21.
He H., Kogut MHCpG-ODN-induced nitric oxide production is mediated through clathrin-dependent endocytosis, endosomal maturation, and activation of PKC, MEK1/2 and p38 MAPK, and NF-κB pathways in avian macrophage cells (HD11). Cell Signal2003; 15: 911-917.
22.
Xie H., Raybourne RB, Babu US et al. CpG-induced immunomodulation and intracellular bacterial killing in a chicken macrophage cell line. Dev Comp Immunol2003; 27: 823-834.
23.
Brownlie R. , Zhu J., Allan B. et al. Chicken TLR21 acts as a functional homologue to mammalian TLR9 in the recognition of CpG oligodeoxynucleotides . Mol Immunol2009; 46: 3163-3170.
24.
Alexopoulou L., Holt AC, Medzhitov R. et al. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature2001; 413: 732-738.
25.
Matsumoto M. , Funami K., Oshiumi H. et al. Toll-like receptor 3: a link between Toll-like receptor, interferon and viruses. Microbiol Immunol2004; 48: 147-154.
26.
Schmidt KN, Leung B., Kwong M. et al. APC-independent activation of NK cells by the Toll-like receptor 3 agonist double-stranded RNA. J Immunol2004 ; 172: 138-143.
27.
Schwarz H., Schneider K., Ohnemus A. et al. Chicken Toll-like receptor 3 recognizes its cognate ligand when ectopically expressed in human cells. J Interferon Cytokine Res2007; 27: 97-101.
28.
Sato S., Nomura F., Kawai T. et al. Synergy and cross-tolerance between Toll-like receptor (TLR) 2- and TLR4-mediated signaling pathways. J Immunol2000; 165: 7096-7101.
29.
Whitmore MM, DeVeer MJ, Edling A. et al. Synergistic activation of innate immunity by double-stranded RNA and CpG DNA promotes enhanced antitumor activity. Cancer Res2004; 64: 5850-5860.
30.
Napolitani G. , Rinaldi A., Bertoni F. et al. Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat Immunol2005; 6: 769-776.
31.
Merlo A., Calcaterra C., Mènard S. et al. Cross-talk between Toll-like receptors 5 and 9 on activation of human immune responses. J Leukoc Biol2007 ; 82: 509-518.
32.
Vanhoutte F., Paget C., Breuilh L. et al. Toll-like receptor (TLR)2 and TLR3 synergy and cross-inhibition in murine myeloid dendritic cells. Immunol Lett2008; 116: 86-94.
33.
Mäkelä SM, Strengell M., Pietilä TE et al. Multiple signaling pathways contribute to synergistic TLR ligand-dependent cytokine gene expression in human monocyte-derived macrophages and dendritic cells. J Leukoc Biol2009; 85: 664-672.
34.
DaMatta RA, Manhaes L., Seabra SH et al. Coculture of chicken thrombocytes and monocytes: morphological changes and lectin binding. Biocell1998; 22: 45-52.
35.
Green L., Wagner D., Glogowski J. et al. Analysis of nitrate, nitrite and [15 N]nitrate in biological fluids . Anal Biochem1982; 126: 131-138.
36.
Livak KJ, Schmittgen TDAnalysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods2001; 25: 402-408.
37.
Netea MG, van der Graaf C., Van der Meer JW et al. Toll-like receptors and the host defense against microbial pathogens: bringing specificity to the innate-immune system. J Leukoc Biol2004; 75: 749-755.
38.
Werling D., Hope JC, Howard CJ et al. Differential production of cytokines, reactive oxygen and nitrogen by bovine macrophages and dendritic cells stimulated with Toll-like receptor agonists. Immunology2004; 111: 41-52.
39.
Werling D., Jungi TWToll-like receptors linking innate and adaptive immune response. Vet Immunol Immunopathol2003; 91: 1-12.
40.
Eisenstein TKImplications of Salmonella-induced nitric oxide (NO) for host defense and vaccines: NO, an antimicrobial, antitumor, immunosuppressive and immunoregulatory molecule. Microb Infect2001; 3: 1223-1231.
41.
Nathan C., Shiloh MUReactive oxygen and nitrogen intermediates in the relationship between hosts and microbial pathogens. Proc Natl Acad Sci IUSA2000; 97: 8841-8848.
42.
Djeraba A., Musset E., Bernardet N. et al. Similar pattern of iNOS expression, NO production and cytokine response in genetic and vaccination-acquired resistance to Marek’s disease . Vet Immunol Immunopathol2002; 85: 63-75.
43.
Swaggerty CL , Pevzner IY, Kaiser P. et al. Profiling pro-inflammatory cytokine and chemokine mRNA expression levels as a novel method for selection of increased innate immune responsiveness. Vet Immunol Immunopathol2008; 126: 35-42.
44.
Kawai T., Akira S.Signaling to NF-kappaB by Toll-like receptors. Trends Mol Med2007; 13: 460-469.
45.
Banerjee A. , Gerondakis S.Coordinating TLR-activated signaling pathways in cells of the immune system. Immunol Cell Biol2007; 85: 420-424.
46.
O’Neill LA, Bowie AGThe family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol2007; 7: 353-364.
47.
Ahmad-Nejad P., Hacker H., Rutz M. et al. Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur J Immunol2002; 32: 1958-1968.
48.
Kajita E., Nishiya T., Miwa S.The transmembrane domain directs TLR9 to intracellular compartments that contain TLR3. Biochem Biophys Res Commun2006; 343: 578-584.
49.
Kim JH, Jeong JH, Jeon ST et al. Decursin inhibits induction of inflammatory mediators by blocking nuclear factor-kappaB activation in macrophages. Mol Pharmacol2006; 69: 1783-1790.
50.
Swaggerty CL , Kaiser P., Rothwell L. et al. Heterophil cytokine mRNA profiles from genetically distinct lines of chickens with differential heterophil-mediated innate immune responses. Avian Pathol2006 ; 35: 102-108.
51.
Gomis S., Babiuk L., Allan B. et al. Protection of chickens against a lethal challenge of Escherichia coli by a vaccine containing CpG oligodeoxynucleotides as an adjuvant. Avian Dis2007; 51: 78-83.
52.
Taghavi A., Allan B., Mutwiri G. et al. Protection of neonatal broiler chicks against Salmonella typhimurium septicemia by DNA containing CpG motifs. Avian Dis2008; 52: 398-406.
53.
Taghavi A., Allan B., Mutwiri G. et al. Enhancement of immunoprotective effect of CpG-ODN by formulation with polyphosphazenes against E. coli septicemia in neonatal chickens. Curr Drug Deliv2009; 6: 76-82.
54.
Mackinnon KM , He H., Swaggerty CL et al. In ovo treatment with CpG oligodeoxynucleotides decreases colonization of Salmonella enteritidis in broiler chickens. Vet Immunol Immunopathol2009; 127: 371-375.
55.
Dar A., Potter A., Tikoo S. et al. CpG oligodeoxynucleotides activate innate immune response that suppresses infectious bronchitis virus replication in chicken embryos. Avian Dis2009; 53: 261-267.
56.
Beadling C. , Slifka MKHow do viral infections predispose patients to bacterial infections?Curr Opin Infect Dis2004; 17: 185-191.
