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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

He, Haiqi, Genovese, Kenneth J., Swaggerty, Christina L., MacKinnon, Kathryn M., Kogut, Michael H.
Developmental and Comparative Immunology 2012 v.36 no.4 pp. 756
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
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.