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Identification of the salmonid IL-17A/F1a/b, IL-17A/F2b, IL-17A/F3 and IL-17N genes and analysis of their expression following in vitro stimulation and infection

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Abstract

This study identifies four new IL-17A/F isoforms in salmonids, as well as IL-17N. IL-17A/F1 and IL-17A/F2 are each represented by two paralogues, with a predicted pseudogene of IL-17N also apparent in the salmonid genome. Analysis of the sequences and genes of the known IL-17A/F and IL-17N molecules suggests that IL-17N is a member within the IL-17A/F subfamily. Analysis of factors that modulated the expression of these genes showed that PHA and PMA were good inducers of salmon IL-17A/F1a and IL-17A/F2a, with rIL-21 a potent stimulator of IL-17A/F1a and IL-17A/F3. The potential involvement of these isoforms during responses post-vaccination and infection was also studied. In unvaccinated control fish, Yersinia ruckeri infection resulted in a marked up-regulation of IL-17A/F1a and IL-17N in the spleen and head kidney and IL-17A/F2a and IL-17A/F3 in the spleen. In the vaccinated fish, only one significant increase was seen relative to control fish, of IL-17A/F2a in the gills, whether the fish were challenged with Y. ruckeri or given the saline placebo. It was also apparent in the gills and head kidney that the level of IL-17A/F1b remained elevated in the Y. ruckeri-challenged fish at a time when it had decreased in saline-injected fish. The relative importance of these isoforms for disease resistance remains to be determined.

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References

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    Article  CAS  PubMed  Google Scholar 

  • Amores A, Catchen J, Ferrara A, Fontenot Q, Postlethwait JH (2011) Genome evolution and meiotic maps by massively parallel DNA sequencing: spotted gar, an outgroup for the teleost genome duplication. Genetics 188:799–808

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Antonysamy MA, Numasaki M (2003) Interleukin-17 (IL-17, IL-25). In: Thomson AW, Lotze MT (eds) The cytokine handbook, 4th edn. Academic, London, pp 475–502

    Chapter  Google Scholar 

  • Berthelot C, Brunet F, Chalopin D, Juanchich A, Bernard M, Noel B, Bento P, Da Silva C, Labadie K, Alberti A, Aury JM, Louis A, Dehais P, Bardou P, Montfort J, Klopp C, Cabau C, Gaspin C, Thorgaard GH, Boussaha M, Quillet E, Guyomard R, Galiana D, Bobe J, Volff JN, Genet C, Wincker P, Jaillon O, Crollius HR, Guiguen Y (2014) The rainbow trout genome provides novel insights into evolution after whole-genome duplication in vertebrates. Nat Commun 5:3657

    Article  PubMed Central  PubMed  Google Scholar 

  • Campanella JJ, Bitincka L, Smalley J (2003) MatGAT: an application that generates similarity/identity matrices using protein or DNA sequences. BMC Bioinform 4:29

    Article  Google Scholar 

  • Chenna R, Sugawara H, Koike T, Lopez R, Gibson TJ, Higgins DG et al (2003) Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res 31:3497–3500

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Costa MM, Maehr T, Diaz-Rosales P, Secombes CJ, Wang T (2011) Bioactivity studies of rainbow trout (Oncorhynchus mykiss) interleukin-6: effects on macrophage growth and antimicrobial peptide gene expression. Mol Immunol 48:1903–1916

    Article  CAS  PubMed  Google Scholar 

  • Costa MM, Pereiro P, Wang T, Secombes CJ, Figueras A, Novoa B (2012) Characterization and gene expression analysis of the two main Th17 cytokines (IL-17A/F and IL-22) in turbot, Scophthalmus maximus. Dev Comp Immunol 38:505–516

    Article  CAS  PubMed  Google Scholar 

  • Davidson WS, Koop BF, Jones SJM, Iturra P, Vidal R, Maass A, Jonassen I, Lien S, Omholt SW (2010) Sequencing the genome of the Atlantic salmon (Salmo salar). Genome Biol 11:403

    PubMed Central  PubMed  Google Scholar 

  • Díaz-Rosales P, Bird S, Wang TH, Fujiki K, Davidson WS, Zou J, Secombes CJ (2009) Rainbow trout interleukin-2: cloning, expression and bioactivity analysis. Fish Shellfish Immunol 27:414–422

    Article  PubMed  Google Scholar 

  • Ely LK, Fischer S, Garcia KC (2009) Structural basis of receptor sharing by interleukin 17 cytokines. Nature Immunol 10:1245–1251

    Article  CAS  Google Scholar 

  • Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, Bairoch A (2005) Protein identification and analysis tools on the ExPASy server. In: Walker JM (ed) The proteomics protocols handbook. Humana, Totowa, pp 571–607

    Chapter  Google Scholar 

  • Gunimaladevi I, Savan R, Sakai M (2006) Identification, cloning and characterization of interleukin-17 and its family from zebrafish. Fish Shellfish Immunol 21:393–403

    Article  CAS  PubMed  Google Scholar 

  • Guo P, Hirano M, Herrin BR, Li J, Yu C, Sadlonova A, Cooper MD (2009) Dual nature of the adaptive immune system in lampreys. Nature 459:796–801

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Harun NO, Wang T, Secombes CJ (2011) Gene expression profiling in naïve and vaccinated rainbow trout after Yersinia ruckeri infection: insights into the mechanisms of protection seen in vaccinated fish. Vaccine 29:4388–4399

    Article  CAS  PubMed  Google Scholar 

  • Hong S, Li R, Xu Q, Secombes CJ, Wang T (2013) Two types of TNF-α exist in teleost fish: phylogenetic, expressional and bioactivity analysis of type II TNF-a3 in rainbow trout Oncorhynchus mykiss. J Immunol 191:5959–5972

    Article  CAS  PubMed  Google Scholar 

  • Hong S, Zou J, Crampe M, Peddie S, Scapigliati G, Bols N, Cunningham C, Secombes CJ (2001) The production and bioactivity of rainbow trout (Oncorhynchus mykiss) recombinant IL-1β. Vet Immunol Immunopathol 81:1–14

    Article  CAS  PubMed  Google Scholar 

  • Husain M, Bird S, van Zwieten R, Secombes CJ, Wang T (2012) Cloning of the IL-1β3 gene and IL-1β4 pseudogene in salmonids uncovers a second type of IL-1β gene in teleost fish. Dev Comp Immunol 38:431–446

    Article  CAS  PubMed  Google Scholar 

  • Husain M, Martin SA, Wang T (2014) Identification and characterisation of the IL-27 p28 subunits in fish: cloning and comparative expression analysis of two p28 paralogues in Atlantic salmon Salmo salar. Fish Shellfish Immunol 41:102–112

    Article  CAS  PubMed  Google Scholar 

  • Hymowitz SG, Filvaroff EH, Yin JP, Lee J, Cai L, Risser P, Maruoka M, Mao W, Foster J, Kelley RF, Pan G, Gurney AL, de Vos AM, Starovasnik MA (2001) IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding. EMBO J 20:5332–5341

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jiang Y, Husain M, Qi Z, Wang T (2015) Identification and expression analysis of two interleukin-23α (p19) isoforms, in rainbow trout Oncorhynchus mykiss and Atlantic salmon Salmo salar. Mol Immunol 66:216–228

    Article  CAS  PubMed  Google Scholar 

  • Jones SA, Sutton CE, Cua D, Mills KHG (2012) Therapeutic potential of targeting IL-17. Nat Immunol 13:1022–1025

    Article  CAS  PubMed  Google Scholar 

  • Khabar KS (2010) Post-transcriptional control during chronic inflammation and cancer: a focus on AU-rich elements. Cell Mol Life Sci 67:2937–2955

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kochetov AV, Ahmad S, Ivanisenko V, Volkova OA, Kolchanov NA, Sarai A (2008) uORFs, reinitiation and alternative translation start sites in human mRNAs. FEBS Lett 582:1293–1297

    Article  CAS  PubMed  Google Scholar 

  • Kono T, Korenaga H, Sakai M (2011) Genomics of fish IL-17 ligand and receptors: a review. Fish Shellfish Immunol 31:635–643

    Article  CAS  PubMed  Google Scholar 

  • Kumari J, Larsen AN, Bogwald J, Dalmo RA (2009) Interleukin-17D in Atlantic salmon (Salmo salar): molecular characterization, 3D modelling and promoter analysis. Fish Shellfish Immunol 27:647–659

  • Korenaga H, Kono T, Sakai M (2010) Isolation of seven IL-17 family genes from the Japanese pufferfish Takifugu rubripes. Fish Shellfish Immunol 28:809–818

    Article  CAS  PubMed  Google Scholar 

  • León B, Lund FE (2013) IL-17-producing B cells combat parasites. Nature Immunol 14:419–421

    Article  Google Scholar 

  • Li J, Zhang Y, Zhang Y, Xiang Z, Tong Y, Qu F, Yu Z (2014) Genomic characterization and expression analysis of five novel IL-17 genes in the Pacific oyster, Crassostrea gigas. Fish Shellfish Immunol 40:455–465

    Article  CAS  PubMed  Google Scholar 

  • Louis A, Muffato M, Roest Crollius H (2013) Genomicus: five genome browsers for comparative genomics in eukaryota. Nucleic Acids Res 41(Database issue):D700–D705

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Macqueen DJ, Johnston IA (2014) A well-constrained estimate for the timing of the salmonid whole genome duplication reveals major decoupling from species diversification. Proc Roy Soc B 281:20132881

    Article  Google Scholar 

  • Marfori M, Mynott A, Ellis JJ, Mehdi AM, Saunders NF, Curmi PM, Forwood JK, Bodén M, Kobe B (2011) Molecular basis for specificity of nuclear import and prediction of nuclear localization. Biochim Biophys Acta 1813:1562–1577

    Article  CAS  PubMed  Google Scholar 

  • McAleer JP, Kolls JK (2014) Directing traffic: IL-17 and IL-22 coordinate pulmonary immune defense. Imm Rev 260:129–144

    Article  CAS  Google Scholar 

  • Meyer A, Van de Peer Y (2005) From 2R to 3R: evidence for a fish-specific genome duplication (FSGD). Bioessays 27:937–945

    Article  CAS  PubMed  Google Scholar 

  • Monte MM, Wang T, Holland JW, Zou J, Secombes CJ (2013) Cloning and characterization of rainbow trout interleukin-17A/F2 (IL-17A/F2) and IL-17 receptor A: expression during infection and bioactivity of recombinant IL-17A/F2. Infect Immun 81:340–353

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mutoloki S, Cooper GA, Marjara IS, Koop BF, Evensen Ø (2010) High gene expression of inflammatory markers and IL-17A correlates with severity of injection site reactions of Atlantic salmon vaccinated with oil-adjuvanted vaccines. BMC Genomics 11:336

    Article  PubMed Central  PubMed  Google Scholar 

  • Petersen TN, Brunak S, von Heijne G, Nielsen H (2011) SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat Methods 8:785–786

    Article  CAS  PubMed  Google Scholar 

  • Qi Z, Jiang Y, Holland JW, Nie P, Secombes CJ, Wang T (2015) Identification and expression analysis of an atypical chemokine receptor-2 (ACKR2)/CC chemokine binding protein-2 (CCBP2) in rainbow trout (Oncorhynchus mykiss). Fish Shellfish Immunol 44:389–398

  • Raida MK, Buchmann K (2008) Bath vaccination of rainbow trout (Oncorhynchus mykiss Walbaum) against Yersinia ruckeri: effects of temperature on protection and gene expression. Vaccine 26:1050–1062

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro CMS, Pontes MJSL, Bird S, Chadzinska M, Scheer M, Verburg-van Kemenade BML, Savelkoul HFJ, Wiegertjes GF (2010) Trypanosomiasis-induced Th17-like immune responses in carp. PLoS ONE 5:e13012

    Article  PubMed Central  PubMed  Google Scholar 

  • Secombes CJ, Wang TH, Bird S (2011) The interleukins of fish. Dev Comp Immunol 35:1336–1345

  • Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 30:2725–2729

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tobback E, Decostere A, Hermans K, Haesebrouck F, Chiers K (2007) Yersinia ruckeri infections in salmonid fish. J Fish Dis 30:257–268

    Article  CAS  PubMed  Google Scholar 

  • Tsutsui S, Nakamura O, Watanabe T (2007) Lamprey (Lethenteron japonicum) IL-17 upregulated by LPS-stimulation in the skin cells. Immunogenetics 59:873–882

    Article  CAS  PubMed  Google Scholar 

  • Venkatesh B et al (2014) Elephant shark genome provides unique insights into gnathostome evolution. Nature 505:174–179

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Vizzini A, Di Falco F, Parrinello D, Sanfratello MA, Mazzarella C, Parrinello N, Cammarata M (2015) Ciona intestinalis interleukin 17-like genes expression is upregulated by LPS challenge. Dev Comp Immunol 48:129–137

    Article  CAS  PubMed  Google Scholar 

  • Wang T, Diaz-Rosales P, Costa MM, Campbell S, Snow M, Collet B, Martin SA, Secombes CJ (2011a) Functional characterization of a nonmammalian IL-21: rainbow trout Oncorhynchus mykiss IL-21 upregulates the expression of the Th cell signature cytokines IFN-gamma, IL-10, and IL-22. J Immunol 186:708–821

    Article  CAS  PubMed  Google Scholar 

  • Wang T, Huang W, Costa MM, Martin SA, Secombes CJ (2011b) Two copies of the genes encoding the subunits of putative interleukin (IL)-4/IL-13 receptors, IL-4Rα, IL-13Rα1 and IL-13Rα2, have been identified in rainbow trout (Oncorhynchus mykiss) and have complex patterns of expression and modulation. Immunogenetics 63:235–253

    Article  CAS  PubMed  Google Scholar 

  • Wang T, Husain M (2014) The expanding repertoire of the IL-12 cytokine family in teleost fish: identification of three paralogues each of the p35 and p40 genes in salmonids, and comparative analysis of their expression and modulation in Atlantic salmon Salmo salar. Dev Comp Immunol 46:194–207

    Article  CAS  PubMed  Google Scholar 

  • Wang T, Husain M, Hong S, Holland JW (2014a) Differential expression, modulation, and bioactivity of distinct fish IL-12 isoforms: implication towards the evolution of Th1-like immune responses. Eur J Immunol 44:1541–1551

    Article  CAS  PubMed  Google Scholar 

  • Wang T, Martin SA, Secombes CJ (2010) Two interleukin-17C-like genes exist in rainbow trout Oncorhynchus mykiss that are differentially expressed and modulated. Dev Comp Immunol 34:491–500

    Article  CAS  PubMed  Google Scholar 

  • Wang T, Secombes CJ (2003) Complete sequencing and expression of three complement components, C1r, C4 and C1 inhibitor, of the classical activation pathway of the complement system in rainbow trout Oncorhynchus mykiss. Immunogenetics 55:615–628

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Li C, Thongda W, Luo Y, Beck B, Peatman E (2014b) Characterization and mucosal responses of interleukin 17 family ligand and receptor genes in channel catfish Ictalurus punctatus. Fish Shellfish Immunol 38:47–55

    Article  CAS  PubMed  Google Scholar 

  • Xu Q, Li R, Monte MM, Jiang Y, Nie P, Holland JW, Secombes CJ, Wang T (2014) Sequence and expression analysis of rainbow trout CXCR2, CXCR3a and CXCR3b aids interpretation of lineage-specific conversion, loss and expansion of these receptors during vertebrate evolution. Dev Comp Immunol 45:201–213

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang H, Shen B, Wu H, Gao L, Liu Q, Wang Q, Xiao J, Zhang Y (2014) Th17-like immune response in fish mucosal tissues after administration of live attenuated Vibrio anguillarum via different vaccination routes. Fish Shellfish Immunol 37:229–238

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

TW received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland) funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions. MH was funded by the Public Authority of Applied Education and Training (KUWAIT). YJ and QX were supported financially by the National Scholarship Council of China. This work was partially supported financially by the European Commission, contract Nos. 222719 (LIFECYCLE) and 311993 (TargetFish).

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Authors and Affiliations

  1. Scottish Fish Immunology Research Centre, Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, AB24 2TZ, UK

    Tiehui Wang, Yousheng Jiang, Alex Wang, Mansourah Husain, Qiaoqing Xu & Christopher J. Secombes

  2. College of Fishery and Life Science, Shanghai Ocean University, Shanghai, 201306, China

    Yousheng Jiang

  3. School of Animal Science, Yangtze University, Jingzhou, 434020, Hubei Province, China

    Qiaoqing Xu

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  1. Tiehui Wang
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  2. Yousheng Jiang
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  3. Alex Wang
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Correspondence to Christopher J. Secombes.

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Wang, T., Jiang, Y., Wang, A. et al. Identification of the salmonid IL-17A/F1a/b, IL-17A/F2b, IL-17A/F3 and IL-17N genes and analysis of their expression following in vitro stimulation and infection. Immunogenetics 67, 395–412 (2015). https://doi.org/10.1007/s00251-015-0838-1

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