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Bovine IFNGR2, IL12RB1, IL12RB2, and IL23R polymorphisms and MAP infection status

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Abstract

Mycobacterium avium ssp. paratuberculosis (MAP) infection causes a chronic granulomatous inflammatory condition of the bovine gut that is characterized by diarrhea, progressive weight loss, and emaciation, and ultimately leads to loss in productivity and profitability of dairy operations. The host cytokine machinery is known to play an important role in protecting against MAP infection. Therefore, the goal of the present study was to assess whether polymorphisms in candidate genes encoding important cytokines and cytokine receptors are associated with MAP infection status of dairy cattle. MAP infection status was evaluated based on serum and milk enzyme-linked immunosorbent assays (ELISAs) for MAP-specific antibodies. Twenty previously reported polymorphisms in genes encoding bovine interferon gamma (IFNG), IFNGR1, IFNGR2, IL22, IL22RA1, IL12RB1, IL12RB2, and IL23R were genotyped in a resource population of 446 dairy Holsteins with known MAP infection status, and logistic regression was used to assess the statistical association with a binomial MAP infection status phenotype. Four SNPs in IFNGR2, IL12RB1, IL12RB2, and IL23R were found to be associated with the MAP infection status of the resource population. These results underscore the importance of cytokines and their receptors in conferring protection against MAP infection and warrant further functional characterization of these associations.

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References

  • Athie-Morales V, Smits HH, Cantrell DA, Hilkens CM (2004) Sustained IL-12 signaling is required for Th1 development. J Immunol 172:61–69

    PubMed  CAS  Google Scholar 

  • Boniface K, Blom B, Liu YJ, de Waal Malefyt R (2008) From interleukin-23 to T-helper 17 cells: human T-helper cell differentiation revisited. Immunol Rev 226:132–146

    Article  PubMed  CAS  Google Scholar 

  • Cetinkaya B, Erdogan HM, Morgan KL (1997) Relationships between the presence of Johne’s disease and farm and management factors in dairy cattle in England. Prev Vet Med 32:253–266

    Article  PubMed  CAS  Google Scholar 

  • Cooper AM, Dalton DK, Stewart TA, Griffin JP, Russell DG, Orme IM (1993) Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med 178:2243–2247

    Article  PubMed  CAS  Google Scholar 

  • Coussens PM (2004) Model for immune responses to Mycobacterium avium subspecies paratuberculosis in cattle. Infect Immun 72:3089–3096

    Article  PubMed  CAS  Google Scholar 

  • Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463

    Article  PubMed  CAS  Google Scholar 

  • Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR (1993) An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178:2249–2254

    Article  PubMed  CAS  Google Scholar 

  • Freedman ML, Reich D, Penney KL, McDonald GJ, Mignault AA, Patterson N, Gabriel SB, Topol EJ, Smoller JW, Pato CN, Pato MT, Petryshen TL, Kolonel LN, Lander ES, Sklar P, Henderson B, Hirschhorn JN, Altshuler D (2004) Assessing the impact of population stratification on genetic association studies. Nat Genet 36:388–393

    Article  PubMed  CAS  Google Scholar 

  • Geisbauer E, Khol JL, Wassertheurer M, Damoser J, Osterreicher E, Dunser M, Revilla-Fernandez S, Baumgartner W (2007) Long-term investigation in an Austrian dairy herd with low prevalence of paratuberculosis detection of antibodies in blood and milk. Vet Q 29:138–148

    PubMed  CAS  Google Scholar 

  • Gonda MG, Chang YM, Shook GE, Collins MT, Kirkpatrick BW (2006) Genetic variation of Mycobacterium avium ssp. paratuberculosis infection in US Holsteins. J Dairy Sci 89:1804–1812

    Article  PubMed  CAS  Google Scholar 

  • Grant IR (2005) Zoonotic potential of Mycobacterium avium ssp. paratuberculosis: the current position. J Appl Microbiol 98:1282–1293

    Article  PubMed  CAS  Google Scholar 

  • Gurney AL (2004) IL-22, a Th1 cytokine that targets the pancreas and select other peripheral tissues. Int Immunopharmacol 4:669–677

    Article  PubMed  CAS  Google Scholar 

  • Ha SJ, Kim DJ, Baek KH, Yun YD, Sung YC (2004) IL-23 induces stronger sustained CTL and Th1 immune responses than IL-12 in hepatitis C virus envelope protein 2 DNA immunization. J Immunol 172:525–531

    PubMed  CAS  Google Scholar 

  • Hunt R, Sauna ZE, Ambudkar SV, Gottesman MM, Kimchi-Sarfaty C (2009) Silent (synonymous) SNPs: Should we care about them? Methods Mol Biol 578:23–39

    Article  PubMed  CAS  Google Scholar 

  • Jakobsen MB, Alban L, Nielsen SS (2000) A cross-sectional study of paratuberculosis in 1155 Danish dairy cows. Prev Vet Med 46:15–27

    Article  PubMed  CAS  Google Scholar 

  • Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM (2007) A “silent” polymorphism in the MDR1 gene changes substrate specificity. Science 315:525–528

    Article  PubMed  CAS  Google Scholar 

  • Koets AP, Adugna G, Janss LL, van Weering HJ, Kalis CH, Wentink GH, Rutten VP, Schukken YH (2000) Genetic variation of susceptibility to Mycobacterium avium subsp. paratuberculosis infection in dairy cattle. J Dairy Sci 83:2702–2708

    Article  PubMed  CAS  Google Scholar 

  • Lauriola M, Ugolini G, Rivetti S, Nani S, Rosati G, Zanotti S, Montroni I, Manaresi A, Zattoni D, Belluzzi A, Castellani L, D’Uva G, Mattei G, Taffurelli M, Strippoli P, Solmi R (2011) IL23R, NOD2/CARD15, ATG16L1 and PHOX2B polymorphisms in a group of patients with Crohn’s disease and correlation with sub-phenotypes. Int J Mol Med 27:469–477

    Article  PubMed  Google Scholar 

  • Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203:2271–2279

    Article  PubMed  CAS  Google Scholar 

  • McGovern DP, Rotter JI, Mei L, Haritunians T, Landers C, Derkowski C, Dutridge D, Dubinsky M, Ippoliti A, Vasiliauskas E, Mengesha E, King L, Pressman S, Targan SR, Taylor KD (2009) Genetic epistasis of IL23/IL17 pathway genes in Crohn’s disease. Inflamm Bowel Dis 15:883–889

    Article  PubMed  Google Scholar 

  • McKenzie BS, Kastelein RA, Cua DJ (2006) Understanding the IL-23-IL-17 immune pathway. Trends Immunol 27:17–23

    Article  PubMed  CAS  Google Scholar 

  • Mikkelsen H, Jungersen G, Nielsen SS (2009) Association between milk antibody and interferon-gamma responses in cattle from Mycobacterium avium subsp. paratuberculosis infected herds. Vet Immunol Immunopathol 127:235–241

    Article  PubMed  CAS  Google Scholar 

  • Mortensen H, Nielsen SS, Berg P (2004) Genetic variation and heritability of the antibody response to Mycobacterium avium subspecies paratuberculosis in Danish Holstein cows. J Dairy Sci 87:2108–2113

    Article  PubMed  CAS  Google Scholar 

  • Murphy MA, Shariflou MR, Moran C (2002) High quality genomic DNA extraction from large milk samples. J Dairy Res 69:645–649

    Article  PubMed  CAS  Google Scholar 

  • Nielsen SS, Toft N (2006) Age-specific characteristics of ELISA and fecal culture for purpose-specific testing for paratuberculosis. J Dairy Sci 89:569–579

    Article  PubMed  CAS  Google Scholar 

  • Nielsen SS, Toft N (2007) Assessment of management-related risk factors for paratuberculosis in Danish dairy herds using Bayesian mixture models. Prev Vet Med 81:306–317

    Article  PubMed  CAS  Google Scholar 

  • Nielsen SS, Toft N (2008) Ante mortem diagnosis of paratuberculosis: a review of accuracies of ELISA, interferon-gamma assay and faecal culture techniques. Vet Microbiol 129:217–235

    Article  PubMed  CAS  Google Scholar 

  • Schulman NF, Viitala SM, de Koning DJ, Virta J, Maki-Tanila A, Vilkki JH (2004) Quantitative trait loci for health traits in Finnish Ayrshire cattle. J Dairy Sci 87:443–449

    Article  PubMed  CAS  Google Scholar 

  • Settles M, Zanella R, McKay SD, Schnabel RD, Taylor JF, Whitlock R, Schukken Y, Van Kessel JS, Smith JM, Neibergs H (2009) A whole genome association analysis identifies loci associated with Mycobacterium avium subsp. paratuberculosis infection status in US Holstein cattle. Anim Genet 40:655–662

    Article  PubMed  CAS  Google Scholar 

  • Trinchieri G (2003) Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Localio R, Rebbeck TR (2005) Bias correction with a single null marker for population stratification in candidate gene association studies. Hum Hered 59:165–175

    Article  PubMed  Google Scholar 

  • Wells SJ, Ott SL, Seitzinger AH (1998) Key health issues for dairy cattle—new and old. J Dairy Sci 81:3029–3035

    Article  PubMed  CAS  Google Scholar 

  • Woodbine KA, Schukken YH, Green LE, Ramirez-Villaescusa A, Mason S, Moore SJ, Bilbao C, Swann N, Medley GF (2009) Seroprevalence and epidemiological characteristics of Mycobacterium avium subsp. paratuberculosis on 114 cattle farms in south west England. Prev Vet Med 89:102–109

    Article  PubMed  Google Scholar 

  • Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, Ouyang W (2007) Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445:648–651

    Article  PubMed  CAS  Google Scholar 

  • Zurbrick BG, Follett DM, Czuprynski CJ (1988) Cytokine regulation of the intracellular growth of Mycobacterium paratuberculosis in bovine monocytes. Infect Immun 56:1692–1697

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Dairy Cattle Genetics Research and Development (DairyGen) Council.

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Authors and Affiliations

  1. Department of Animal and Poultry Science, Centre for Genetic Improvement of Livestock, University of Guelph, Guelph, ON, N1G 2W1, Canada

    Sameer D. Pant, Chris P. Verschoor, Alicia M. Skelding, Flavio S. Schenkel, Qiumei You, Graham A. Biggar & Niel A. Karrow

  2. Population Medicine, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada

    David F. Kelton

  3. Department of Animal and Poultry Science, University of Guelph, 50 Stone Road East, Building # 70, Room 123, Guelph, ON, N1G 2W1, Canada

    Niel A. Karrow

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  1. Sameer D. Pant
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  2. Chris P. Verschoor
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  3. Alicia M. Skelding
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  4. Flavio S. Schenkel
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  5. Qiumei You
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  8. Niel A. Karrow
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Correspondence to Niel A. Karrow.

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Pant, S.D., Verschoor, C.P., Skelding, A.M. et al. Bovine IFNGR2, IL12RB1, IL12RB2, and IL23R polymorphisms and MAP infection status. Mamm Genome 22, 583–588 (2011). https://doi.org/10.1007/s00335-011-9332-8

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  • DOI: https://doi.org/10.1007/s00335-011-9332-8

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