Immunogenetics

, Volume 61, Issue 2, pp 153–160 | Cite as

Differences in distribution of single nucleotide polymorphisms among intracellular pattern recognition receptors in pigs

  • Chihiro Kojima-Shibata
  • Hiroki Shinkai
  • Takeya Morozumi
  • Kosuke Jozaki
  • Daisuke Toki
  • Toshimi Matsumoto
  • Hiroshi Kadowaki
  • Eisaku Suzuki
  • Hirohide Uenishi
Brief Communication

Abstract

Pathogens localized extracellularly or incorporated into endosomes are recognized mainly by Toll-like receptors, whereas pathogens and pathogen-derived molecules that invade into the cytoplasm of host cells typically are recognized by intracellular pattern recognition receptors (PRRs), such as retinoic acid-inducible gene (RIG)-like helicases (RLHs) and nucleotide-binding oligmerization domain (NOD)-like receptors (NLRs). RIG-I and melanoma differentiation-associated gene 5 (MDA5), which belong to the RLH family, recognize viral genomic RNA, whereas NOD2, a member of the NLR family, responds to microbial peptidoglycans. These receptors may play an important role in pig opportunistic infectious diseases, such as pneumonia and diarrhea, which markedly impair livestock productivity, such that polymorphisms of these receptor genes are potential targets of pig breeding to increase disease resistance. Here, we report single nucleotide polymorphisms (SNPs) in porcine DDX58, IFIH1, and NOD2, which encode RIG-I, MDA5, and NOD2, respectively. Interestingly, compared with DDX58 and IFIH1, NOD2 abounded in nonsynonymous SNPs both throughout the coding sequence and in sequences encoding domains important for ligand recognition, such as helicase domains for RIG-I and MDA5 and leucine-rich repeats in NOD2. These differences in the distribution of SNPs in intracellular PRRs may parallel the diversity of their ligands, which include nucleic acids and peptidoglycans.

Keywords

Pattern recognition receptor (PRR) Single nucleotide polymorphism (SNP) Helicase domain Leucine-rich repeat (LRR) Swine 

Notes

Acknowledgments

This work was supported by the Animal Genome Research Project of the Ministry of Agriculture, Forestry and Fisheries of Japan and by a Grant-in-Aid from the Japan Racing Association.

Supplementary material

251_2008_350_MOESM1_ESM.doc (152 kb)
ESM 1 (DOC 152 kb)

References

  1. Biberstein EL, Hirsh DC (1999) Staphylococci. In: Hirsh DC, Zee Y-C (eds) Veterinary microbiology. Blackwell, Oxford, UK, p 115−119Google Scholar
  2. Bowie AG, Fitzgerald KA (2007) RIG-I: tri-ing to discriminate between self and non-self RNA. Trends Immunol 28:147–150. doi: 10.1016/j.it.2007.02.002 PubMedCrossRefGoogle Scholar
  3. Cargill EJ, Womack JE (2007) Detection of polymorphisms in bovine toll-like receptors 3, 7, 8, and 9. Genomics 89:745–755. doi: 10.1016/j.ygeno.2007.02.008 PubMedCrossRefGoogle Scholar
  4. Ewing B, Green P (1998) Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res 8:186–194. doi: 10.1101/gr.8.3.186 PubMedGoogle Scholar
  5. Ewing B, Hillier L, Wendl MC, Green P (1998) Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res 8:175–185. doi: 10.1101/gr.8.3.175 PubMedGoogle Scholar
  6. Girardin SE, Boneca IG, Viala J, Chamaillard M, Labigne A, Thomas G, Philpott DJ, Sansonetti PJ (2003) Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 278:8869–8872. doi: 10.1074/jbc.C200651200 PubMedCrossRefGoogle Scholar
  7. Gordon D, Abajian C, Green P (1998) Consed: a graphical tool for sequence finishing. Genome Res 8:195–202. doi: 10.1101/gr.8.3.195 PubMedGoogle Scholar
  8. Hornung V, Ellegast J, Kim S, Brzózka K, Jung A, Kato H, Poeck H, Akira S, Conzelmann KK, Schlee M, Endres S, Hartmann G (2006) 5′-Triphosphate RNA is the ligand for RIG-I. Science 314:994–997. doi: 10.1126/science.1132505 PubMedCrossRefGoogle Scholar
  9. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, Almer S, Tysk C, O’Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411:599–603. doi: 10.1038/35079107 PubMedCrossRefGoogle Scholar
  10. Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster SJ, Moran AP, Fernandez-Luna JL, Nuñez G (2003) Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease. J Biol Chem 278:5509–5512. doi: 10.1074/jbc.C200673200 PubMedCrossRefGoogle Scholar
  11. Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, Paik SG, Lee H, Lee JO (2007) Crystal structure of the TLR1–TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 130:1071–1082. doi: 10.1016/j.cell.2007.09.008 PubMedCrossRefGoogle Scholar
  12. Jungerius BJ, Gu J, Crooijmans RP, van der Poel JJ, Groenen MA, van Oost BA, te Pas MF (2005) Estimation of the extent of linkage disequilibrium in seven regions of the porcine genome. Anim Biotechnol 16:41–54. doi: 10.1081/ABIO-200053402 PubMedCrossRefGoogle Scholar
  13. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ, Yamaguchi O, Otsu K, Tsujimura T, Koh CS, Reis e Sousa C, Matsuura Y, Fujita T, Akira S (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101–105. doi: 10.1038/nature04734 PubMedCrossRefGoogle Scholar
  14. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S (2005) IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol 6:981–988. doi: 10.1038/ni1243 PubMedCrossRefGoogle Scholar
  15. Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ, Lee JO (2007) Crystal structure of the TLR4–MD-2 complex with bound endotoxin antagonist Eritoran. Cell 130:906–917. doi: 10.1016/j.cell.2007.08.002 PubMedCrossRefGoogle Scholar
  16. Ma X, Liu Y, Gowen BB, Graviss EA, Clark AG, Musser JM (2007) Full-exon resequencing reveals toll-like receptor variants contribute to human susceptibility to tuberculosis disease. PLoS One 2:e1318. doi: 10.1371/journal.pone.0001318 PubMedCrossRefGoogle Scholar
  17. Maeda S, Hsu LC, Liu H, Bankston LA, Iimura M, Kagnoff MF, Eckmann L, Karin M (2005) Nod2 mutation in Crohn’s disease potentiates NF-κB activity and IL-1β processing. Science 307:734–738. doi: 10.1126/science.1103685 PubMedCrossRefGoogle Scholar
  18. Martinon F, Tschopp J (2005) NLRs join TLRs as innate sensors of pathogens. Trends Immunol 26:447–454. doi: 10.1016/j.it.2005.06.004 PubMedCrossRefGoogle Scholar
  19. Medzhitov R, Janeway CA Jr (2002) Decoding the patterns of self and nonself by the innate immune system. Science 296:298–300. doi: 10.1126/science.1068883 PubMedCrossRefGoogle Scholar
  20. Meylan E, Tschopp J, Karin M (2006) Intracellular pattern recognition receptors in the host response. Nature 442:39–44. doi: 10.1038/nature04946 PubMedCrossRefGoogle Scholar
  21. Nickerson DA, Tobe VO, Taylor SL (1997) PolyPhred: automating the detection and genotyping of single nucleotide substitutions using fluorescence-based resequencing. Nucleic Acids Res 25:2745–2751. doi: 10.1093/nar/25.14.2745 PubMedCrossRefGoogle Scholar
  22. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nuñez G, Cho JH (2001a) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411:603–606. doi: 10.1038/35079114 PubMedCrossRefGoogle Scholar
  23. Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nuñez G (2001b) Nod2, a Nod1/Apaf-1 family member that is restricted to monocytes and activates NF-κB. J Biol Chem 276:4812–4818. doi: 10.1074/jbc.M008072200 PubMedCrossRefGoogle Scholar
  24. Okumura N, Hayashi T, Sekikawa H, Matsumoto T, Mikawa A, Hamasima N, Awata T (2005) Sequences and mapping of genes encoding porcine tyrosinase (TYR) and tyrosinase-related proteins (TYRP1 and TYRP2). Anim Genet 36:513–516. doi: 10.1111/j.1365-2052.2005.01353.x PubMedCrossRefGoogle Scholar
  25. Okumura N, Matsumoto T, Hamasima N, Awata T (2008) Single nucleotide polymorphisms of the KIT and KITLG genes in pigs. Anim Sci J 79:303–313. doi: 10.1111/j.1740-0929.2008.00531.x CrossRefGoogle Scholar
  26. Pichlmair A, Schulz O, Tan CP, Näslund TI, Liljeström P, Weber F, Reis e Sousa C (2006) RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 314:997–1001. doi: 10.1126/science.1132998 PubMedCrossRefGoogle Scholar
  27. Seabury CM, Cargill EJ, Womack JE (2007) Sequence variability and protein domain architectures for bovine Toll-like receptors 1, 5, and 10. Genomics 90:502–515. doi: 10.1016/j.ygeno.2007.07.001 PubMedCrossRefGoogle Scholar
  28. Shinkai H, Tanaka M, Morozumi T, Eguchi-Ogawa T, Okumura N, Muneta Y, Awata T, Uenishi H (2006) Biased distribution of single nucleotide polymorphisms (SNPs) in porcine Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR5, and TLR6 genes. Immunogenetics 58:324–330. doi: 10.1007/s00251-005-0068-z PubMedCrossRefGoogle Scholar
  29. Smyth DJ, Cooper JD, Bailey R, Field S, Burren O, Smink LJ, Guja C, Ionescu-Tirgoviste C, Widmer B, Dunger DB, Savage DA, Walker NM, Clayton DG, Todd JA (2006) A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Nat Genet 38:617–619. doi: 10.1038/ng1800 PubMedCrossRefGoogle Scholar
  30. Sutherland A, Davies J, Owen CJ, Vaikkakara S, Walker C, Cheetham TD, James RA, Perros P, Donaldson PT, Cordell HJ, Quinton R, Pearce SH (2007) Genomic polymorphism at the interferon-induced helicase (IFIH1) locus contributes to Graves’ disease susceptibility. J Clin Endocrinol Metab 92:3338–3341. doi: 10.1210/jc.2007-0173 PubMedCrossRefGoogle Scholar
  31. Takeda K, Akira S (2005) Toll-like receptors in innate immunity. Int Immunol 17:1–14. doi: 10.1093/intimm/dxh186 PubMedCrossRefGoogle Scholar
  32. Tanaka M, Suzuki K, Morozumi T, Kobayashi E, Matsumoto T, Domukai M, Eguchi-Ogawa T, Shinkai H, Awata T, Uenishi H (2006) Genomic structure and gene order of swine chromosome 7q1.1→q1.2. Anim Genet 37:10–16. doi: 10.1111/j.1365-2052.2005.01362.x PubMedCrossRefGoogle Scholar
  33. Tohno M, Ueda W, Azuma Y, Shimazu T, Katoh S, Wang JM, Aso H, Takada H, Kawai Y, Saito T, Kitazawa H (2008) Molecular cloning and functional characterization of porcine nucleotide-binding oligomerization domain-2 (NOD2). Mol Immunol 45:194–203. doi: 10.1016/j.molimm.2007.04.019 PubMedCrossRefGoogle Scholar
  34. Watanabe T, Kitani A, Murray PJ, Strober W (2004) NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol 5:800–808. doi: 10.1038/ni1092 PubMedCrossRefGoogle Scholar
  35. White SN, Taylor KH, Abbey CA, Gill CA, Womack JE (2003) Haplotype variation in bovine Toll-like receptor 4 and computational prediction of a positively selected ligand-binding domain. Proc Natl Acad Sci U S A 100:10364–10369. doi: 10.1073/pnas.1333957100 PubMedCrossRefGoogle Scholar
  36. Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M Jr, Akira S, Yonehara S, Kato A, Fujita T (2005) Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 175:2851–2858PubMedGoogle Scholar
  37. Zhang X, Wang C, Schook LB, Hawken RJ, Rutherford MS (2000) An RNA helicase, RHIV -1, induced by porcine reproductive and respiratory syndrome virus (PRRSV) is mapped on porcine chromosome 10q13. Microb Pathog 28:267–278. doi: 10.1006/mpat.1999.0349 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Chihiro Kojima-Shibata
    • 1
  • Hiroki Shinkai
    • 2
    • 3
  • Takeya Morozumi
    • 2
    • 3
  • Kosuke Jozaki
    • 2
    • 4
    • 5
    • 6
  • Daisuke Toki
    • 2
    • 3
  • Toshimi Matsumoto
    • 2
    • 3
  • Hiroshi Kadowaki
    • 1
  • Eisaku Suzuki
    • 1
  • Hirohide Uenishi
    • 2
    • 4
  1. 1.Miyagi Livestock Experimental Station, Miyagi PrefectureOsakiJapan
  2. 2.Animal Genome Research ProgramNIAS/STAFFTsukubaJapan
  3. 3.Second Research DivisionInstitute of Society for Techno-innovation of Agriculture, Forestry and Fisheries (STAFF-Institute)TsukubaJapan
  4. 4.Division of Animal SciencesNational Institute of Agrobiological Sciences (NIAS)TsukubaJapan
  5. 5.United Graduate School of Agricultural SciencesKagoshima UniversitySagaJapan
  6. 6.Graduate School of AgricultureSaga UniversitySagaJapan

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