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Co-stimulation with TLR3 and TLR21 ligands synergistically up-regulates Th1-cytokine IFN-gamma and regulatory cytokine IL-10 expression in chicken monocytes

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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-a and IFN-b, Th1 cytokines IFN-c 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-c, IL-10, and IL-12p40, but not IFN-a and IFN-b; whereas poly I:C induced the expression of INF-c, IFN-a, IFN-b, 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-c 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.
Haiqi He , Kenneth J. Genovese , Christina L. Swaggerty , Kathryn M. MacKinnon , Michael H. Kogut
agonists , bacterial infections , chemokines , chickens , double-stranded RNA , gene expression , immune response , interferon-gamma , interleukin-10 , interleukin-12 , interleukin-4 , mammals , messenger RNA , monocytes , nitric oxide , receptors , synergism , vaccine adjuvants , vaccine development , viral diseases of animals and humans
Developmental and Comparative Immunology 2011 v.36
Journal Articles, USDA Authors, Peer-Reviewed
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