Changes in some pro-and anti-inflammatory cytokines produced by bovine peripheral blood mononuclear cells following foot and mouth disease vaccination

Document Type: Short Communication

Authors

1 Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

2 Department of Immunology, Qazvin University of Medical Sciences, Qazvin, Iran

Abstract

Interleukin (IL)-17 is exclusively produced by CD4 helper T-cells upon activation. It most often acts as a pro-inflammatory cytokine, which stimulates the release of pro-inflammatory cytokines IL-6, IL-8, TNF-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF). In this study, we studied the in-vitro IL-17 response to specific antigens and a variety of mitogens and compared the IL-17 response to IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-γ responses. We used a foot and mouth disease (FMD) vaccine as specific antigens and mitogens (phytohemagglutinin [PHA], pokeweed mitogen [PWM], and concanavalin A [Con A]) to stimulate peripheral blood mononuclear cells (PBMCs) of vaccinated calves. Cell culture supernatant was harvested and analyzed for cytokines, using commercially available bovine ELISA kits. The mitogens induced a significant increase in IL-17 production. IL-17 was produced at high levels in response to the T cell-stimulated mitogens, PHA, and Con A, and at low levels in response to PWM mitogens. In contrast, level of the produced IL-17 cytokines in response to the FMDV antigens was lower as compared to those produced by mitogens. The FMDV antigens and mitogens significantly increased IL-17 production. There was not a correlation between IL-17 production and type-1 cytokine, IFN-γ, and IL-2, while there was a correlation between type-2 cytokine, IL-4, and IL-5 at either cytokine level produced by PBMCs stimulated by FMDV antigens. Moreover, there was an interaction between IL-17 and IL-6, that is, as IL-6 cytokine level elevated or diminished, IL-17 cytokine level increased or decreased, as well.

Keywords

Main Subjects


Article Title [French]

Modifications dans certaines cytokines pro- et anti-inflammatoires libérées par les cellules mononucléées du sang périphérique des bovins après une vaccination contre la fièvre aphteuse

Abstract [French]

L’interleukine (IL)-17 est exclusivement produite par les cellules T auxiliaires CD4 après activation. L’IL-17 agit le plus souvent comme une cytokine pro-inflammatoire capable de stimuler la libération d’autres cytokines pro-inflammatoires (IL-6, IL-8, TNF-α) ainsi que les facteurs de stimulation des colonies de granulocytes-macrophage (GM-CSF). Dans cette étude, nous avons étudié la réponse in vitro IL-17 vis-à-vis d’antigènes spécifiques et d’une série de substances mitogènes. La réponse IL-17 a été ensuite comparée à celles d’autres cytokines, en l’occurrence l’IL-2, IL-4, IL-5, IL-6, IL-10, et l’IFN-γ. Dans ce but, les antigènes spécifiques du vaccin de la fièvre aphteuse (foot and mouth disease vaccine, FMDV) et des substances mitogènes comme la phytohémagglutinine (PHA), l’agent mitogène de la phytolaque (pokeweed mitogen, PWM) ainsi que la concanavaline A (Con A) ont été utilisés dans le but de stimuler les cellules mononucléées du sang périphérique (PBMC) des veaux vaccinés. Le surnageant des cultures cellulaires a été prélevé et son contenu en cytokines analysé en utilisant des kits ELISA bovins commerciaux. Selon nos résultats, les agents mitogènes induisent une hausse significative de la libération d’IL-17. Des taux élevés de cette cytokine sont effectivement produits à la suite d’une stimulation des cellules T par la PHA et la Con A alors que la réponse au mitogène PWM semble moins importante. En revanche, letaux d’IL-17 généré en réponse des antigènes spécifiques du FMDV est bien inférieur comparé à ceux induits par les mitogènes. Les antigènes FMDV et les substances mitogènes testées augmentent donc de façon significative la production IL-17. Il n’y a cependant pas de corrélation entre la libération d’IL-17 et la concentration des cytokines de type 1 « IFN-γ, et IL-2 », contrairement au cas des cytokines de type 2 « IL-4 et IL-5 » dont la production par les PBMC est stimulée par les antigènes FMDV. De plus, un lien direct a été établi entre les taux des cytokines IL-17 et IL-6 libérés lors des différentes stimulations.

Keywords [French]

  • Interleukine-17
  • Vaccin
  • Fièvre Aphteuse
  • Cellules mononucléées du sang périphériques

Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T.B., Oukka, M., Weiner, H.L., Kuchroo, V.K., 2006. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441, 235-238.

Chabaud, M., Durand, J.M., Buchs, N., Fossiez, F., Page, G., Frappart, L., Miossec, P., 1999. Human interleukin-17: A T cell–derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis & Rheumatism 42, 963-970.

Cua, D.J., Tato, C.M., 2010. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 10, 479-489.

Daenicke, S., Keese, C., Goyarts, T., Döll, S., 2011. Effects of deoxynivalenol (DON) and related compounds on bovine peripheral blood mononuclear cells (PBMC) in vitro and in vivo. Mycotoxin Research 27, 49-55.

Dong, C., Flavell, R.A., 2000. Cell fate decision: T-helper 1 and 2 subsets in immune responses. Arthritis Res 2, 179-188.

Espir, T., Tibery, s., Figueira, L.d.P., Naiff, M.d.F., da Costa, A.G., #xe3, es, Ramalho-Ortig, #xe3, o, M., Malheiro, A., Franco, A.M.R., 2014. The Role of Inflammatory, Anti-Inflammatory, and Regulatory Cytokines in Patients Infected with Cutaneous Leishmaniasis in Amazonas State, Brazil. Journal of Immunology Research 2014, 10.

Fossiez, F., Djossou, O., Chomarat, P., Flores-Romo, L., Ait-Yahia, S., Maat, C., Pin, J.J., Garrone, P., Garcia, E., Saeland, S., Blanchard, D., Gaillard, C., Das Mahapatra, B., Rouvier, E., Golstein, P., Banchereau, J., Lebecque, S., 1996. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. The Journal of Experimental Medicine 183, 2593-2603.

Harrington, L.E., Hatton, R.D., Mangan, P.R., Turner, H., Murphy, T.L., Murphy, K.M., Weaver, C.T., 2005. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6, 1123-1132.

Iwakura, Y., Ishigame, H., 2006. The IL-23/IL-17 axis in inflammation. J Clin Invest 116, 1218-1222.

Jin, W., Dong, C., 2013. IL-17 cytokines in immunity and inflammation. Emerg Microbes Infect 2, e60.

Jovanovic, D.V., Di Battista, J.A., Martel-Pelletier, J., Jolicoeur, F.C., He, Y., Zhang, M., Mineau, F., Pelletier, J.P., 1998. IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol 160, 3513-3521.

Kondo, T., Sugiura, T., Kamada, M., Imagawa, H., 1996. Colorimetric Assay of Equine Peripheral Lymphocyte Blastogenesis Using MTT. Journal of Equine Science 7, 63-66.

Korn, T., Bettelli, E., Oukka, M., Kuchroo, V.K., 2009. IL-17 and Th17 Cells. Annu Rev Immunol 27, 485-517.

Kurtzhals, J.A.L., Hansen, M.B., Hey, A.S., Poulsen, L.K., 1992. Measurement of antigen-dependent interleukin-4 production by human peripheral blood mononuclear cells Introduction of an amplification step using ionomycin and phorbol myristate acetate. Journal of Immunological Methods 156, 239-245.

Lenarczyk, A., Helsloot, J., Farmer, K., Peters, L., Sturgess, A., Kirkham, B., 2000. Antigen-induced IL-17 response in the peripheral blood mononuclear cells (PBMC) of healthy controls. Clin Exp Immunol 122, 41-48.

Li, Y., Simons, F.E., HayGlass, K.T., 1998. Environmental antigen-induced IL-13 responses are elevated among subjects with allergic rhinitis, are independent of IL-4, and are inhibited by endogenous IFN-gamma synthesis. J Immunol 161, 7007-7014.

Mangan, P.R., Harrington, L.E., O'Quinn, D.B., Helms, W.S., Bullard, D.C., Elson, C.O., Hatton, R.D., Wahl, S.M., Schoeb, T.R., Weaver, C.T., 2006. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441, 231-234.

Miller, R.A., Flurkey, K., Molloy, M., Luby, T., Stadecker, M.J., 1991. Differential sensitivity of virgin and memory T lymphocytes to calcium ionophores suggests a buoyant density separation method and a model for memory cell hyporesponsiveness to Con A. J Immunol 147, 3080-3086.

Mills, K.H., 2008. Induction, function and regulation of IL-17-producing T cells. Eur J Immunol 38, 2636-2649.

Mingala, C.N., Konnai, S., Venturina, F.A., Onuma, M., Ohashi, K., 2009. Quantification of water buffalo (Bubalus bubalis) cytokine expression in response to inactivated foot-and-mouth disease (FMD) vaccine. Res Vet Sci 87, 213-217.

Morimoto, C., Letvin, N.L., Boyd, A.W., Hagan, M., Brown, H.M., Kornacki, M.M., Schlossman, S.F., 1985. The isolation and characterization of the human helper inducer T cell subset. J Immunol 134, 3762-3769.

Park, H., Li, Z., Yang, X.O., Chang, S.H., Nurieva, R., Wang, Y.H., Wang, Y., Hood, L., Zhu, Z., Tian, Q., Dong, C., 2005. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6, 1133-1141.

Rašková, G., Kovářů, F., Bártová, J., 2005. Cytokine production by porcine mononuclear leukocytes stimulated by mitogens. Acta Veterinaria Brno 74, 521-525.

Simon, M.M., Hochgeschwender, U., Brugger, U., Landolfo, S., 1986. Monoclonal antibodies to interferon-gamma inhibit interleukin 2-dependent induction of growth and

maturation in lectin/antigen-reactive cytolytic T lymphocyte precursors. J Immunol 136, 2755-2762.

Veldhoen, M., Hocking, R.J., Atkins, C.J., Locksley, R.M., Stockinger, B., 2006. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24, 179-189.

Vincent, F.B., Northcott, M., Hoi, A., Mackay, F., Morand, E.F., 2013. Clinical associations of serum interleukin-17 in systemic lupus erythematosus. Arthritis Res Ther 15, R97.

Yao, Z., Painter, S.L., Fanslow, W.C., Ulrich, D., Macduff, B.M., Spriggs, M.K., Armitage, R.J., 1995. Human IL-17: a novel cytokine derived from T cells. J Immunol 155, 5483-5486.

Zhu, S., Qian, Y., 2012. IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. Clin Sci (Lond) 122, 487-511.