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Toll-like receptor ligands and their combinations as adjuvants - current research and its relevance in chickens

Published online by Cambridge University Press:  10 March 2015

S.K. GUPTA ,
L.V. SINGH ,
M.M. CHELLAPPA  and
S. DEY
S.K. GUPTA*
Affiliation:
Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly-243122 (U.P.), India
L.V. SINGH
Affiliation:
Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly-243122 (U.P.), India
M.M. CHELLAPPA
Affiliation:
Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly-243122 (U.P.), India
S. DEY
Affiliation:
Division of Veterinary Biotechnology, Indian Veterinary Research Institute, Izatnagar, Bareilly-243122 (U.P.), India
*
Corresponding author: shishirgupta.biotech@gmail.com
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Abstract

With the advancement in knowledge of innate immune functioning, toll-like receptors (TLRs) have emerged as potential adjuvant candidates. TLRs are one of the types of pattern recognition receptors (PRRs) that sense conserved signature molecules on invading pathogens. Detection of the pathogens via TLRs alerts the immune system of the host and helps in mounting a quick immune response against the invading pathogens. This property of TLR ligands may be exploited for the development of effective prophylactic agents against infectious chicken diseases. In this review the immunostimulatory effects of various TLRs will be discussed as well as their use as adjuvants in combination.

Keywords

chickenTLRsadjuvantTLR combinationssynergyantagonismcross-talk
Type
Reviews
Information
World's Poultry Science Journal , Volume 71 , Issue 1 , March 2015 , pp. 95 - 110
Copyright
Copyright © World's Poultry Science Association 2015 

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References

ADACHI, O., KAWAI, T., TAKEDA, K., MATSUMOTO, M., TSUTSUI, H., SAKAGAMI, M., NAKANISHI K. and AKIRA, S. (1998) Targeted Disruption of the MyD88 Gene Results in Loss of IL-1-and IL-18-Mediated Function. Immunity 9: 143-150.Google Scholar
AKIRA, S., TAKEDA, K. and KAISHO, T. (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nature Immunology2: 675-680.Google Scholar
AKIRA, S., UEMATSU, S. and TAKEUCHI, O. (2006) Pathogen recognition and innate immunity. Cell 124: 783-801.CrossRefGoogle ScholarPubMed
ALEXOPOULOU, L., HOLT, A.C., MEDZHITOV, R. and FLAVELL, R.A. (2001) Recognition of doublestranded RNA and activation of NF-kB by Toll-like receptor 3. Nature 413: 732-738.Google Scholar
BEUTLER, E., GELBART, T. and WEST, C. (2001) Synergy between TLR2 and TLR4: a safety mechanism. Blood Cells Molecules and Diseases 27: 728-730.CrossRefGoogle ScholarPubMed
BEUTLER, B., JIANG, Z., GEORGEL, P., CROZAT, K., CROKER, B., RUTSCHMANN, S., DU, X. and HOEBE, K. (2006) Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large. Annual Review of Immunology 24: 353-389.Google Scholar
BOOTH, J.S., BUZA, J.J., POTTER, A., BABIUK, L.A. and MUTWIRI, G.K. (2010) Co-stimulation with TLR7/8 and TLR9 agonists induce down-regulation of innate immune responses in sheep blood mononuclear and B cells. Developmental and Comparative Immunology 34: 572-578.Google Scholar
BOYD, A.C., PEROVAL, M.Y., HAMMOND, J.A., PRICKETT, M.D., YOUNG, J.R. and SMITH, A.L. (2012) TLR15 is unique to avian and reptilian lineages and recognises a yeast-derived agonist. The Journal of Immunology 189: 4930-4938.Google Scholar
BROWNLIE, R., ZHU, J., ALLAN, B., MUTWIRI, G.K., BABIUK, L.A., POTTER, A. and GRIEBEL, P. (2009) Chicken TLR21 acts as a functional homologue to mammalian TLR9 in the recognition of CpG oligodeoxynucleotides. Molecular Immunology 46: 3163-3170.Google Scholar
CHOW, J.C., YOUNG, D.W., GOLENBOCK, D.T., CHRIST, W.J. and GUSOVSUREDSKY, F. (1999) Toll-like receptor-4 mediates lipopolysaccharide the induced signal transduction. Journal of Biological Chemistry 274: 10689-10692.Google Scholar
DAR, A., POTTER, A., TIKOO, S., GERDTS, V., LAI, K., BABIUK, L.A. and MUTWIRI, G. (2009) CpG oligodeoxynucleotides activate innate immune response that suppresses infectious bronchitis virus replication in chicken embryos. Avian diseases 53: 261-267.Google Scholar
DE NARDO, D., DE NARDO, C.M., NGUYEN, T., HAMILTON, J.A. and SCHOLZ, G.M. (2009) Signaling crosstalk during sequential TLR4 and TLR9 activation amplifies the inflammatory response of mouse macrophages. The Journal of Immunology 183: 8110-8118.Google Scholar
DE ZOETE, M.R., BOUWMAN, L.I., KEESTRA, A.M. and VAN PUTTEN, J.P. (2011) Cleavage and activation of a Toll-like receptor by microbial proteases. Proceedings of the National Academy of Sciences 108: 4968-4973.CrossRefGoogle ScholarPubMed
DIEBOLD, S.S., KAISHO, T., HEMMI, H., AKIR, S. and REIS E SOUSA, C. (2004) Innate antiviral responses by means of TLR7-mediated recognition of single stranded RNA. Science 303: 1529-1531.Google Scholar
FARNELL, M.B., CRIPPEN, T.L., HE, H., SWAGGERTY, C.L. and KOGUT, M.H. (2003) Oxidative burst mediated by toll like receptors (TLR) and CD14 on avian heterophils stimulated with bacterial toll agonists. Developmental and Comparative Immunology 27: 423-429.Google Scholar
FRANCHI, L., AMER, A., BODY-MALAPEL, M., KANNEGANTI, T.D., ÖZÖREN, N., JAGIRDAR, R., INOHARA, N. 1, VANDENABEELE, P., BERTIN, J., COYLE, A., GRANT, E.P. and NUNEZ, G. (2006) Cytosolic flagellin requires Ipaf for activation of caspase-1 and interleukin 1β in salmonella-infected macrophages. Nature Immunology 7 (6): 576-582.Google Scholar
FRITZ, J.H., FERRERO, R.L., PHILPOTT, D.J. and GIRARDIN, S.E. (2006) Nod-like proteins in immunity, inflammation and disease. Nature Immunology 12: 1250-1257.Google Scholar
GAO, J.J., ZUVANICH, E.G., XUE, Q., HORN, D.L., SILVERSTEIN, R. and MORRISON, D.C. (1999) Cutting edge: bacterial DNA and LPS act in synergy in inducing nitric oxide production in RAW 264.7 macrophages. The Journal of Immunology 163: 4095-4099.Google Scholar
GAO, J.J., XUE, Q., PAPASIAN, C.J. and MORRISON, D.C. (2001) Bacterial DNA and lipopolysaccharide induce synergistic production of TNF-alpha through a post-transcriptional mechanism. The Journal of Immunology 166: 6855-6860.Google Scholar
GHOSH, T.K., MICKELSON, D.J., SOLBERG, J.C., LIPSON, K.E., INGLEFIELD, J.R. and ALKAN, S.S. (2007) TLR-TLR cross talk in human PBMC resulting in synergistic and antagonistic regulation of type-1 and 2 interferons, IL-12 and TNF-α. International immunopharmacology 7: 1111-1121.Google Scholar
GUPTA, S.K., BAJWA, P., DEB, R., MOHAN, C.M. and DEY, S. (2014a) Flagellin- A TLR5 agonist as an adjuvant in chicken vaccines. Clinical and Vaccine Immunology 21 (3): 261-270.CrossRefGoogle Scholar
GUPTA, S.K., DEB, R., DEY, S. and CHELLAPPA, M.M. (2014) Toll-like receptor-based adjuvants: enhancing the immune response to vaccines against infectious diseases of chicken. Expert review of vaccines 13 (7): 909-925.Google Scholar
GUPTA, S.K., DEB, R., GAIKWAD, S., SARAVANAN, R., MOHAN, C.M. and DEY, S. (2013) Recombinant flagellin and its cross-talk with lipopolysaccharide-Effect on pooled chicken peripheral blood mononuclear cells. Research in Veterinary Science 95: 930-935.Google Scholar
GURJAR, R.S., GULLEY, S.L. and VAN GINKEL, F.W. (2013) Cell-mediated immune responses in the head-associated lymphoid tissues induced to a live attenuated avian coronavirus vaccine. Developmental and Comparative Immunology 41: 715-722.Google Scholar
HAWN, T.R., VERBON, A., LETTINGA, K.D., ZHAO, L.P., LI, S.S., LAWS, R.J., SKERRETT, S.J., BEUTLER, B., SCHROEDER, L., NACHMAN, A., OZINSKY, A., SMITH, K.D. and ADEREM, A. (2003) A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease. The Journal of Experimental Medicine 198 (10): 1563-1572.Google Scholar
HE, H., GENOVESE, K.J., NISBET, D.J. and KOGUT, M.H. (2006) Profile of Toll-like receptor expressions and induction of nitric oxide synthesis by Toll-like receptor agonists in chicken monocytes. Molecular Immunology 43: 783-789.Google Scholar
HE, H., GENOVESE, K.J., NISBET, D.J. and KOGUT, M.H. (2007) Synergy of CpG oligodeoxynucleotide and double-stranded RNA (poly I:C) on nitric oxide induction in chicken peripheral blood monocytes. Molecular Immunology 44: 3234-3242.Google Scholar
HE, H., GENOVESE, K.J., SWAGGERTY, C.L., MACKINNON, K.M. and KOGUT, M.H. (2012) Co-stimulation with TLR3 and TLR21 ligands synergistically up-regulates Th1-cytokine IFN-γ and regulatory cytokine IL-10 expression in chicken monocytes. Developmental and Comparative Immunology 36: 756-760.Google Scholar
HE, H., MACKINNON, K.M., GENOVESE, K.J. and KOGUT, M.H. (2011) CpG oligodeoxynucleotides and double-stranded RNA synergize to enhance nitric oxide production and mRNA expression of inducible nitric oxide synthase, proinflammatory cytokines and chemokines in chicken monocytes. Innate Immunology 17: 137-144.Google Scholar
HEIL, F., AHMAD-NEJAD, P., HEMMI, H., HOCHREIN, H., AMPENBERGER, F., GELLERT, T., DIETRICH, H., LIPFORD, G., TAKEDA, K., AKIRA, S., WAGNER, H. and BAUER, S. (2003) The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily. European Journal of Immunology 33: 2987-2997.Google Scholar
HIGGS, R., CORMICAN, P., CAHALANE, S., ALLAN, B., LLOYD, A.T., MEADE, K., JAMES, T., LYNN, D.J., BABIUK, L.A. and O'FARRELLY, C. (2006) Induction of a novel chicken Toll-like receptor following Salmonella enterica serovar Typhimurium infection. Infection and Immunity 74: 1692-1698.Google Scholar
HIGUCHI, M., MATSUO, A., SHINGAI, M., SHIDA, K., ISHII, A., FUNAMI, K., SUZUKI, Y., OSHIUMI, H., MATSUMOTO, M. and SEYA, T. (2008) Combinational recognition of bacterial lipoproteins and peptidoglycan by chicken Toll-like receptor 2 subfamily. Developmental and Comparative Immunology 32: 147-155.Google Scholar
ICHINOHE, T., WATANABE, I., ITO, S., FUJII, H., MORIYAMA, M., TAMURA, S.I., TAKAHASHI, H., SAWA, H., CHIBA, J., KURATA, T., SATA, T. and HASEGAWA, H. (2005) Synthetic double-stranded RNA poly (I: C) combined with mucosal vaccine protects against influenza virus infection. Journal of Virology 7: 2910-2919.Google Scholar
IQBAL, M., PHILBIN, V.J. and SMITH, A.L. (2005a) Expression patterns of chicken Toll like receptor mRNA in tissues, immune cell subsets, and cell lines. Veterinary Immunology and Immunopathology 104: 117-127.Google Scholar
IQBAL, M., PHILBIN, V.J., WITHANAGE, G.S.K., WIGLEY, P., BEAL, R.K., GOODCHILD, M.J., BARROW, P., MCCONNELL, I., MASKELL, D.J., YOUNG, J., BUMSTEAD, N., BOYD, Y. and SMITH, A.L. (2005b) Identification and functional characterisation of chicken toll-like receptor 5 reveals a fundamental role in the biology of infection with Salmonella enterica serovar typhimurium. Infection and Immunity 73: 2344-2350.Google Scholar
JANEWAY, C.A. Jr and MEDZHITOV, R. (2002) Innate immune recognition. Annual Review of Immunology 20: 197-216.Google Scholar
JENKINS, K.A., LOWENTHAL, J.W., KIMPTON, W. and BEAN, A.G.D. (2009) The in vitro and in ovo responses of chickens to TLR9 subfamily ligands. Developmental and Comparative Immunology 33: 660-667.Google Scholar
KARPALA, A.J., LOWENTHAL, J.W. and BEAN, A.G. (2008) Activation of the TLR3 pathway regulates IFN β production in chickens. Developmental and Comparative Immunology 32: 435-444.Google Scholar
KAWAI, T. and AKIRA, S. (2006) TLR signaling. Cell Death and Differentiation 13: 816-825.Google Scholar
KEESTRA, A.M., DE ZOETE, M.R., VAN AUBEL, R.A. and VAN PUTTEN, J.P. (2007) The central leucine-rich repeat region of chicken TLR16 dictates unique ligand specificity and species-specific interaction with TLR2. The Journal of Immunology 178: 7110-7119.Google Scholar
KEESTRA, A.M., DE ZOETE, M.R., BOUWMAN, L.I. and VAN PUTTEN, J.P. (2010) Chicken TLR21 is an innate CpG DNA receptor distinct from mammalian TLR9. Journal of Immunology 185: 460-467.Google Scholar
KEESTRA, A.M., DE ZOETE, M.R., VAN AUBEL, R.A. and VAN PUTTEN, J.P. (2008) Functional characterisation of chicken TLR5 reveals species-specific recognition of flagellin. Molecular Immunology 45: 1298-1307.Google Scholar
KEESTRA, A.M. and VAN PUTTEN, J.P. (2008) Unique properties of the chicken TLR4/MD-2 complex: selective lipopolysaccharide activation of the MyD88-dependent pathway. Journal of Immunology 181: 4354-4362.Google Scholar
KHALIFEH, M.S., AMAWI, M.M., ABU-BASHA, E.A. and YONIS, I.B. (2009) Assessment of humoral and cellular-mediated immune response in chickens treated with tilmicosin, florfenicol, or enrofloxacin at the time of Newcastle disease vaccination. Poultry Science 88: 2118-2124.Google Scholar
KOGUT, M.H., IQBAL, M., HE, H., PHILBIN, V., KAISER, P. and SMITH, A. (2005) Expression and function of Toll-like receptors in chicken heterophils. Developmental and Comparative Immunology 29: 791-807.Google Scholar
KOGUT, M.H., SWAGGERTY, C., HE, H., PEVZNER, I. and KAISER, P. (2006) Toll-like receptor agonists stimulate differential functional activation and cytokine and chemokine gene expression in heterophils isolated from chickens with differential innate responses. Microbes and Infection 8: 1866-1874.CrossRefGoogle ScholarPubMed
LEVEQUE, G., FORGETTA, V., MORROLL, S., SMITH, A.L., BUMSTEAD, N., BARROW, P., LOREDO-OSTI, J.C., MORGAN, K. and MALO, D. (2003) Allelic variation in TLR4 is linked to susceptibility to Salmonella enterica serovar Typhimurium infection in chickens. Infection and Immunity 71: 1116-1124.Google Scholar
LOTZ, M., EBERT, S., ESSELMANN, H., ILIEV, A.I., PRINZ, M. and WIAZEWICZ, N. (2005) Amyloid beta peptide 1-40 enhances the action of Toll-like receptor-2 and -4 agonists but antagonises Toll-like receptor-9- induced inflammation in primary mouse microglial cell cultures. Journal of Neurochemistry 94: 289-298.Google Scholar
MARSHALL, J.D., HEEKE, D.S., GESNER, M.L., LIVINGSTON, B. and VAN NEST, G. (2007) Negative regulation of TLR9-mediated IFN-α induction by a small-molecule, synthetic TLR7 ligand. Journal of Leukocyte Biology 82: 497-508.Google Scholar
MERLO, A., CALCATERRA, C., MÈNARD, S. and BALSARI, A. (2007) Cross-talk between Toll-like receptors 5 and 9 on activation of human immune responses. Journal of Leukocyte Biology 82: 509-518.Google Scholar
MOGENSEN, T.H. (2009) Pathogen recognition and inflammatory signaling in innate immune defences. Clinical Microbiology Reviews 22: 240-273.Google Scholar
MOLOFSKY, A.B., BYRNE, B.G., WHITFIELD, N.N., MADIGAN, C.A., FUSE, E.T., TATEDA, K. and and SWANSON, M.S. (2006) Cytosolic recognition of flagellin by mouse macrophages restricts Legionella pneumophila infection. The Journal of Experimental Medicine 203 (4): 1093-1104.Google Scholar
NAPOLITANI, G., RINALDI, A., BERTONI, F., SALLUSTO, F. and LANZAVECCHIA, A. (2005) Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nature immunology 6: 769-776.Google Scholar
NERREN, J.R., HE, H., GENOVESE, K. and KOGUT, M.H. (2010) Expression of the avian-specific toll-like receptor 15 in chicken heterophils is mediated by gram-negative and gram-positive bacteria, but not TLR agonists. Veterinary Immunology and Immunopathology 136: 151-156.Google Scholar
NICKERSON, K.M., CHRISTENSEN, S.R., SHUPE, J., KASHGARIAN, M., KIM, D., ELKON, K. and SHLOMCHIK, M.J. (2010) TLR9 regulates TLR7-and MyD88-dependent autoantibody production and disease in a murine model of lupus. The journal of Immunology 184: 1840-1848.Google Scholar
PARMENTIER, H.K., VAN DEN KIEBOOM, W.J., NIEUWLAND, M.G., REILINGH, G.D.V., HANGALAPURA, B.N., SAVELKOUL, H.F. and LAMMERS, A. (2004) Differential effects of lipopolysaccharide and lipoteichoic acid on the primary antibody response to keyhole limpet hemocyanin of chickens selected for high or low antibody responses to sheep red blood cells. Poultry Science 83: 1133-1139.Google Scholar
PATEL, B.A., GOMIS, S., DAR, A., WILLSON, P.J., BABIUK, L.A., POTTER, A., MUTWIRI, G. and TIKOO, S.K. (2008) Oligodeoxynucleotides containing CpG motifs (CpG-ODN) predominantly induce Th1-type immune response in neonatal chicks. Developmental and Comparative Immunology 32: 1041-1049.Google Scholar
PATHAK, S.K., BASU, S., BASU, K.K., BANERJEE, A., PATHAK, S., BHATTACHARYYA, A., KAISHO, T., KUNDU, M. and BASU, J. (2007) Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages. Nature immunology 8: 610-618.Google Scholar
PHILBIN, V.J., IQBAL, M., BOYD, Y., GOODCHILD, M.J., BEAL, R.K., BUMSTEAD, N., YOUNG, J. and SMITH, A.L. (2005) Identification and characterisation of a functional, alternatively spliced Toll-like receptor 7 (TLR7) and genomic disruption of TLR8 in chickens. Immunology 114: 507-521.Google Scholar
ROELOFS, M.F., ABDOLLAHI-ROODSAZ, S., VAN LIESHOUT, A.W.T., SPRONG, T., VAN DEN HOOGEN, F.H., VAN DEN BERG, W.B. and RADSTAKE, T.R.D.J. (2005) The expression of toll-like receptors 3 and 7 in rheumatoid arthritis synovium is increased and costimulation of toll-like receptors 3, 4, and 7/8 results in synergistic cytokine production by dendritic cells. Arthritis and Rheumatism 52: 2313-2322.Google Scholar
RUAN, W.K. and ZHENG, S.J. (2011) Polymorphisms of chicken toll-like receptor 1 type 1 and type 2 in different breeds. Poultry Science 90: 1941-1947.Google Scholar
SANTIAGO-RABER, M.L., DUNAND-SAUTHIER, I., WU, T., LI, Q.Z., UEMATSU, S., AKIRA, S., REITH, W., MOHAN, C., KOTZIN, B.L. and IZUI, S. (2010) Critical role of TLR7 in the acceleration of systemic lupus erythematosus in TLR9-deficient mice. Journal of Autoimmunity 34: 339-348.Google Scholar
SATO, S., NOMURA, F., KAWAI, T., TAKEUCHI, O., MÜHLRADT, P.F., TAKEDA, K. and AKIRA, S. (2000) Synergy and cross-tolerance between toll-like receptor (TLR) 2-and TLR4-mediated signaling pathways. The Journal of Immunology 165: 7096-7101.Google Scholar
SCHWANDNER, R., DZIARSKI, R., WESCHE, H., ROTHE, M. and KIRSCHNING, C.J. (1999) Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. Journal of Biological Chemistry 274: 17406-17409.Google Scholar
SCHWARZ, H., SCHNEIDER, . K, OHNEMUS, A., LAVRIC, M., KOTHLOW, S., BAUER, S., KASPERS, B. and STAEHELI, P. (2007) Chicken toll-like receptor 3 recognises its cognate ligand when ectopically expressed in human cells. Journal of Interferons and Cytokines Research 27: 97-101.Google Scholar
SHAW, M.H., REIMER, T., KIM, Y.G. and NUNEZ, G. (2008) NOD-like receptors (NLRs): bonafide intracellular microbial sensors. Current Opinion in Immunology 20 (4): 377-382.Google Scholar
SHI, Z., CAI, Z., SANCHEZ, A., ZHANG, T., WEN, S., WANG, J., YANG, J., FU, S. and ZHANG, D. (2011) A novel Toll-like receptor that recognises vesicular stomatitis virus. Journal of Biological Chemistry 286: 4517-4524.Google Scholar
SIJBEN, J.W., KLASING, K.C., SCHRAMA, J.W., PARMENTIER, H.K., VAN DER POEL, J.J., SAVELKOUL, H.F. and KAISER, P. (2003) Early in vivo cytokine genes expression in chickens after challenge with Salmonella typhimurium lipopolysaccharide and modulation by dietary n 3 polyunsaturated fatty acids. Developmental and Comparative Immunology 27: 611-619.Google Scholar
SMITH, K.D., ANDERSEN-NISSEN, E., HAYASHI, F., STROBE, K., BERGMAN, M.A., BARRETT, S.L.R., COOKSON, B.T. and ADEREM, A. (2003) Toll-like receptor 5 recognises a conserved site on flagellin required for protofilament formation and bacterial motility. Nature Immunology 4: 1247-1253.Google Scholar
ST. PAUL, M., MALLICK, A.I., HAQ, K., OROUJI, S., ABDUL-CAREEM, M.F. and SHARIF, S. (2011) In vivo administration of ligands for chicken toll-like receptors 4 and 21 induces the expression of immune system genes in the spleen. Veterinary Immunology and Immunopathology 144: 228-237.Google Scholar
ST. PAUL, M., PAOLUCCI, S., BARJESTEH, N., WOOD, R.D. and SHARIF, S. (2013) Chicken erythrocytes respond to Toll-like receptor ligands by up-regulating cytokine transcripts. Research in Veterinary Science 95: 87-91.Google Scholar
ST. PAUL, M., PAOLUCCI, S. and SHARIF, S. (2012a) Treatment with Ligands for Toll-Like Receptors 2 and 5 Induces a Mixed T-helper 1-and 2-Like Response in Chicken Splenocytes. Journal of Interferon Cytokine Research 32: 592-598.Google Scholar
PAUL, M.S., PAOLUCCI, S., BARJESTEH, N., WOOD, R.D., SCHAT, K.A. and SHARIF, S. (2012b) Characterisation of chicken thrombocyte responses to Toll-like receptor ligands. PloS one 7: e43381.Google Scholar
RE, F. and STROMINGER, J.L. (2004) IL-10 released by concomitant TLR2 stimulation blocks the induction of a subset of Th1 cytokines that are specifically induced by TLR4 or TLR3 in human dendritic cells. The Journal of Immunology 173: 7548-7555.Google Scholar
SWAGGERTY, C.L., HE, H., GENOVESE, K.J., DUKE, S.E. and KOGUT, M.H. (2012) Loxoribine pre-treatment reduces Salmonella Enteritidis organ invasion in 1-day-old chickens. Poultry Science 91: 1038-1042.Google Scholar
TAKEDA, K. and AKIRA, S. (2004) TLR signaling pathways. Seminars in Immunology 16: 3-9.CrossRefGoogle ScholarPubMed
TAKESHITA, F., LEIFER, C.A., GURSEL, I., ISHII, K.J., TAKESHITA, S. and GURSEL, M. (2001) Cutting edge: role of Toll-like receptor 9 in CpG DNA-induced activation of human cells. Journal of Immunology 167: 3555-3558.Google Scholar
TOSHCHAKOV, V., JONES, B.W., PERERA, P.Y., THOMAS, K. and CODY, M.J. (2002) TLR4, but not TLR2, mediates IFN-c-induced STAT1-dependent gene expression in macrophages. Nature Immunology 3: 392-398.Google Scholar
VANHOUTTE, F., PAGET, C., BREUILH, L., FONTAINE, J., VENDEVILLE, C., GORIELY, S., RYFFEL, B. and FAVEEUW, C. (2008) Toll-like receptor (TLR) 2 and TLR3 synergy and cross-inhibition in murine myeloid dendritic cells. Immunology Letters 116: 86-94.Google Scholar
VILLANUEVA, A.I., KULKARNI, R.R. and SHARIF, S. (2011) Synthetic double-stranded RNA oligonucleotides are immunostimulatory for chicken spleen cells. Developmental and Comparative Immunology 35: 28-34.Google Scholar
WARGER, T., OSTERLOH, P., RECHTSTEINER, G., FASSBENDER, M., HEIB, V., SCHMID, B., SCHMITT, E., SCHILD, H. and RADSAK, M.P. (2006) Synergistic activation of dendritic cells by combined Toll-like receptor ligation induces superior CTL responses in vivo. Blood 108: 544-550.Google Scholar
WHITMORE, M.M., DEVEER, M.J., EDLING, A., OATES, R.K., SIMONS, B., LINDNER, D. and WILLIAMS, B.R. (2004) Synergistic activation of innate immunity by double-stranded RNA and CpG DNA promotes enhanced antitumor activity. Cancer Research 64: 5850-5860.Google Scholar
YAMAMOTO, M., SATO, S., HEMMI, H., HOSHINO, K., KAISHO, T., SANJO, H., TAKEUCHI, O., SUGIYAMA, M., OKABE, M., TAKEDA, K. and AKIRA, S. (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301: 640-643.Google Scholar
YAMAMOTO, M., SATO, S., MORI, K., HOSHINO, K., TAKEUCHI, O., TAKEDA, K. and AKIRA, S. (2002) Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-β promoter in the Toll-like receptor signaling. The Journal of Immunology 169: 6668-6672.CrossRefGoogle Scholar
YILMAZ, A., SHEN, S., ADELSON, D.L., XAVIER, S. and ZHU, J.J. (2005) Identification and sequence analysis of chicken Toll-like receptors. Immunogenetics 56: 743-753.Google Scholar
YONEYAMA, M., KIKUCHI, M., MATSUMOTO, K., IMAIZUMI, T., MIYAGISHI, M., TAIRA, K., FOY, E., LOO, Y., GALE, M., AKIRA, S., YONEHARA, S., KATO, S. and FUJITA, T. (2005) Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. Journal of Immunology 175 (5): 2851-2858.Google Scholar
YONEYAMA, M., KIKUCHI, M., NATSUKAWA, T., SHINOBU, N., IMAIZUMI, T., MIYAGISHI, M, TAIRA, K., AKIRA, S. and FUJITA, T. (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA induced innate antiviral responses. Nature Immunology 5 (7): 730-737.Google Scholar
ZHOU, Z.Y., WANG, Z.Y., CAO, L.T., HU, S.J., ZHANG, Z., QIN, B., GUO, Z.L. and NIE, K. (2013) Upregulation of chicken TLR4, TLR15 and MyD88 in heterophils and monocyte-derived macrophages stimulated with Eimeria tenella in vitro. Experimental Parasitology 133: 427-433.Google Scholar
ZHU, Q., EGELSTON, C., GAGNON, S., SUI, Y., BELYAKOV, I.M., KLINMAN, D.M. and BERZOFSKY, J. A. (2010) Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in mice. The Journal of Clinical Investigation 120: 607.Google Scholar
ZHU, Q., EGELSTON, C., VIVEKANANDHAN, A., UEMATSU, S., AKIRA, S., KLINMAN, D.M., BELYAKOV, I.M. and BERZOFSKY, J.A. (2008) Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: implications for vaccines. Proceedings of the National Academy of Sciences 105: 16260-16265.Google Scholar