title: Co-stimulation with TLR3 and TLR21 ligands synergistically up-regulates Th1-cytokine IFN-γ and regulatory cytokine IL-10 expression in chicken monocytes.
abstract: Toll-like receptors (TLRs) are pattern recognition receptors of the innate immune system for various conserved pathogen-associated molecular motifs. Chicken TLR3 and TLR21 (avian equivalent to mammalian TLR9) recognize poly I:C (double-stranded RNA) and CpG-ODN (a CpG-motif containing oligodeoxydinucleotide), respectively. Interaction between TLR3 and TLR21 agonists poly I:C and CpG-ODN has been reported to synergize in expression of proinflammatory cytokines and chemokines and the production of nitric oxide in chicken monocytes. However, the interaction between poly I:C and CpG-ODN on the expression of interferons (IFNs) and Th1/Th2 cytokines remains unknown. The objective of the present study was to investigate the effect of the interaction between poly I:C and CpG-ODN on the mRNA expression levels of IFN-α and IFN-β, Th1 cytokines IFN-γ and IL-12, Th2 cytokine IL-4, and regulatory IL-10 in chicken monocytes. When stimulated with either agonist alone, CpG-ODN significantly up-regulated the expression of INF-γ, IL-10, and IL-12p40, but not IFN-α and IFN-β; whereas poly I:C induced the expression of INF-γ, IFN-α, IFN-β, and IL-10; but not IL-12p40. However, stimulation with a combinatory CpG-ODN and poly I:C further synergistically increased the expression of IFN-γ and IL-10 mRNA. Our results provide strong evidence supporting the critical role of TLR3 and TLR21 in avian innate immunity against both viral and bacterial infections; and the synergistic interaction between the TLR3 and TLR21 pathways produces a stronger Th1-biased immune response in chicken monocytes. Our result also suggest a potential use of poly I:C and CpG-ODN together as a more efficient adjuvant for poultry vaccine development.
authors: Southern Plains Agricultural Research Center, USDA-ARS, College Station, TX 77845, USA. haiqi.he@ars.usda.gov
authors: Haiqi
authors: H
authors: He
authors: Kenneth J
authors: KJ
authors: Genovese
authors: Christina L
authors: CL
authors: Swaggerty
authors: Kathryn M
authors: KM
authors: MacKinnon
authors: Michael H
authors: MH
authors: Kogut
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000276:immunology*; D018899:CpG Islands; D007370:Interferon Type I / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009000:Monocytes / Q000378:metabolism*; D009841:Oligonucleotides / Q000276:immunology; D011070:Poly I-C / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology; D014612:Vaccines / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D030161:Avian Proteins; D007370:Interferon Type I; D009841:Oligonucleotides; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D014612:Vaccines; D016753:Interleukin-10; D007371:Interferon-gamma; D011070:Poly I-C