Skip to main content
Log in

Polymorphisms in toll-like receptor (TLR) 1, 4, 9 and SLC11A1 genes and their association with paratuberculosis susceptibility in Holstein and indigenous crossbred cattle in Turkey

  • Research Article
  • Published:
Journal of Genetics Aims and scope Submit manuscript

Abstract

Mycobacterium avium subsp. paratuberculosis (MAP) causes major problem in a wide range of animal species. In ruminant livestock including cattle, it causes a chronic disease called Johne’s disease, or paratuberculosis (pTB) which is currently considered as potential zoonosis, causing Crohn’s disease in humans. MAP infection susceptibility is suspected to be controlled by host genetics. Thus, selecting individuals according to their genetic structure could help to obtain bovine populations that are increasingly resistant to MAP infection. The aim of the present work was to investigate the association between toll-like receptor (TLR) \({ 1}\) (+1380 G/A), TLR1 (+1446 C/A), TLR4 (+10 C/T), TLR9 (+1310 G/A) and solute carrier family 11 member 1 (SLC11A1) (+1066 C/G) mutations and MAP infection status in 813 cattle comprising East Anatolian Red crossbred, Anatolian Black crossbred and Holstein breed. TLR1 (+1380 G/A) mutation showed an association with bovine MAP (\(P\!<\!0.05\)). For the TLR1 (+1380 G/A) locus, the odds ratio for AG and AA genotypes versus GG genotypes were 2.31 (1.24–4.30; 95% confidence interval (CI)) and 0<0.001 (<0.001 to >999.999; 95% CI) which indicated that a proportion of AG homozygote was significantly higher in pTB-affected animals as compared with the control. General linear model analysis demonstrated higher MAP antibody response in TLR1 (+1380 AG) genotype as compared with TLR1 (+1380 GG) (\(P\!<\! 0.0001\)). Present findings suggest that selection against TLR1 (+1380 G/A) may reduce the risk of pTB in bovine herds.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Akira S., Takeda K. and Kaisho T. 2001 Toll-like receptors: critical proteins linking innate and acquired immunity. Nat. Immunol. 2, 675–680.

    Article  CAS  Google Scholar 

  • Arpaia N, Godec J, Lau L, Sivick K. E., McLaughlin L. M., Jones M. B. et al. 2011 TLR signaling is required for Salmonella typhimurium virulence. Cell 144, 675–688.

    Article  CAS  Google Scholar 

  • Bishop S. C. 2015 Genetic resistance to infections in sheep. Vet. Microbiol. 181, 2–7.

    Article  CAS  Google Scholar 

  • Bishop S. C. and Woolliams J. A. 2014 Genomics and disease resistance studies in livestock. Livest. Sci. 166, 190–198.

    Article  Google Scholar 

  • Blackwell J. M., Goswami T., Evans, C. A. W., Sibthorpe D., Papo N., White J. K. et al. 2001 SLC11A1 (formerly NRAMP1) and disease resistance. Cell. Microbiol. 3, 773–784.

    Article  CAS  Google Scholar 

  • Cetinkaya B., Erdogan H. M. and Morgan K. L. 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  CAS  Google Scholar 

  • Chaubey K. K., Gupta R. D., Gupta S., Singh S. V., Bhatia A. K., Jayaraman S. et al. 2016 Trends and advances in the diagnosis and control of paratuberculosis in domestic livestock. Vet. Q. 36, 203–227.

    Article  Google Scholar 

  • Cho J., Tauer L. W., Schukken Y. H., Gómez M. I. Smith R. L., Lu Z. et al. 2012 Economic analysis of Mycobacterium avium subspecies paratuberculosis vaccines in dairy herds. J. Dairy Sci. 95, 1855–1872.

    Article  CAS  Google Scholar 

  • Collins M. T. 2011 Diagnosis of paratuberculosis. Vet. Clin. North Am. Food Anim. Pract. 27, 581–591.

    Article  Google Scholar 

  • Elzo M. A., Rae D. O., Lanhart S. E., Wasdin J. G., Dixon W. P. and Jones J. L. 2006 Factors associated with ELISA scores for paratuberculosis in an Angus-Brahman multibreed herd of beef cattle. J. Anim. Sci. 84, 41–48.

    Article  CAS  Google Scholar 

  • Fecteau M. E. 2018 Paratuberculosis in cattle. Vet. Clin. North Am. Food Anim. Pract. 34, 209–222.

    Article  Google Scholar 

  • Fisher C. A., Bhattarai E. K., Osterstock J. B., Dowd S. E., Seabury P. M., Vikram M. et al. 2011 Evolution of the bovine TLR gene family and member associations with Mycobacterium avium subspecies paratuberculosis infection. PLoS One 6, e27744.

    Article  CAS  Google Scholar 

  • Hinger M., Brandt H. and Erhardt G. 2008 Heritability estimates for antibody response to Mycobacterium avium subspecies paratuberculosis in German Holstein cattle. J. Dairy Sci. 91, 3237–3244.

    Article  CAS  Google Scholar 

  • Juste R. A. 2012 Current strategies for eradication of paratuberculosis and issues in public health. Vet. Immunol. Immunopathol. 148, 16–22.

    Article  Google Scholar 

  • Kirkpatrick B. W. and Shook G. E. 2011 Genetic susceptibility to paratuberculosis. Vet. Clin. North Am. Food Anim. Pract. 27, 559–571.

    Article  Google Scholar 

  • Kirkpatrick B. W., Shi X., Shook G. E. and Collins M. T. 2011 Whole-genome association analysis of susceptibility to paratuberculosis in Holstein cattle. Anim. Genet. 42, 149–160.

    Article  CAS  Google Scholar 

  • Koets A., Santema W., Mertens H., Oostenrijk D., Keestra M., Overdijk M. et al. 2010 Susceptibility to paratuberculosis infection in cattle is associated with single nucleotide polymorphisms in Toll-like receptor 2 which modulate immune responses against Mycobacterium avium subspecies paratuberculosis. Prev. Vet. Med. 93, 305–315.

    Article  CAS  Google Scholar 

  • Lin B. Z., Sasazaki S. and Mannen H. 2010 Genetic diversity and structure in Bos taurus and Bos indicus populations analyzed by SNP markers. Anim. Sci. J. 81, 281–289.

    Article  CAS  Google Scholar 

  • Marcé C., Ezanno P., Weber M. F., Seegers H., Pfeiffer D. U. and Fourichon C. 2010 Invited review: modeling within-herd transmission of Mycobacterium avium subspecies paratuberculosis in dairy cattle: a review. J. Dairy Sci. 93, 4455–4470.

    Article  Google Scholar 

  • Meuwissen T., Hayes B. and Goddard M. 2013 Accelerating improvement of livestock with genomic selection. Annu. Rev. Anim. Biosci. 1, 221–237.

    Article  Google Scholar 

  • Misch E. A., Macdonald M., Ranjit C., Sapkota B. R., Wells R. D., Siddiqui M. R. et al. 2008 Human TLR1 deficiency is associated with impaired mycobacterial signaling and protection from leprosy reversal reaction. PLoS Neglected Trop. Dis. 2, e231.

    Article  Google Scholar 

  • Mortensen H., Nielsen S. S. and 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  CAS  Google Scholar 

  • Mucha R., Bhide M. R., Chakurkar E. B., Novak M. and Mikula I. 2009 Toll-like receptors TLR1, TLR2 and TLR4 gene mutations and natural resistance to Mycobacterium avium subsp. paratuberculosis infection in cattle. Vet. Immunol. Immunopathol. 128, 381–388.

    Article  CAS  Google Scholar 

  • Nielsen D. M. and Weir B. S. 2001 Association studies under general disease models. Theor. Popul. Biol. 60, 253–263.

    Article  CAS  Google Scholar 

  • Pinedo P. J., Buergelt C. D., Donovan G. A., Melendez P., Morel L., Wu R. et al. 2009 Candidate gene polymorphisms (BoIFNG, TLR4, SLC11A1) as risk factors for paratuberculosis infection in cattle. Prev. Vet. Med. 91, 189–196.

    Article  Google Scholar 

  • Pinedo P. J., Galvão K. N. and Seabury C. M. 2013 Innate immune gene variation and differential susceptibility to uterine diseases in Holstein cows. Theriogenology 80, 384–390.

    Article  CAS  Google Scholar 

  • Prakash O., Kumar A., Sonwane A., Rathore R., Singh R. V., Chauhan A. et al. 2014 Polymorphism of cytokine and innate immunity genes associated with bovine brucellosis in cattle. Mol. Biol. Rep. 41, 2815–2825.

    Article  CAS  Google Scholar 

  • Randhawa I. A. S., Khatkar M. S., Thomson P. C. and Raadsma H. W. 2016 A meta-assembly of selection signatures in cattle. PLoS One 11, e0153013.

    Article  Google Scholar 

  • Roussel A. J., Libal M. C., Whitlock R. L., Hairgrove T. B., Barling K. S. and Thompson J. A. 2005 Prevalence of and risk factors for paratuberculosis in purebred beef cattle. J. Am. Vet. Med. Assoc. 226, 773–778.

    Article  Google Scholar 

  • Ruiz-Larrañaga O., Garrido J. M., Manzano C., Iriondo M., Molina E., Gil A. et al. 2010 Identification of single nucleotide polymorphisms in the bovine solute carrier family 11 member 1 (SLC11A1) gene and their association with infection by Mycobacterium avium subspecies paratuberculosis. J. Dairy Sci. 93, 1713–1721.

    Article  Google Scholar 

  • Ruiz-Larrañaga O., Manzano C., Iriondo M., Garrido J. M., Molina E., Vazquez P. et al. 2011 Genetic variation of toll-like receptor genes and infection by Mycobacterium avium ssp. paratuberculosis in Holstein-Friesian cattle. J. Dairy Sci. 94, 3635–3641.

    Article  Google Scholar 

  • Smith R. L., Al-Mamun M. A. and Gröhn, Y. T. 2017 Economic consequences of paratuberculosis control in dairy cattle: a stochastic modeling study. Prev. Vet. Med. 138, 17–27.

    Article  CAS  Google Scholar 

  • Sun L., Song Y., Riaz H., Yang H., Hua G., Guo A. et al. 2012 Polymorphisms in toll-like receptor 1 and 9 genes and their association with tuberculosis susceptibility in Chinese Holstein cattle. Vet. Immunol. Immunopathol. 147, 195–201.

    Article  CAS  Google Scholar 

  • Sweeney R. W., Collins M. T., Koets A. P., McGuirk S. M. and Roussel A. J. 2012 Paratuberculosis (Johne’s disease) in cattle and other susceptible species. J. Vet. Intern. Med. 26, 1239–1250.

    Article  CAS  Google Scholar 

  • Takeda K. and Akira S. 2005 Toll-like receptors in innate immunity. Int. Immunol. 17, 1–14.

    Article  CAS  Google Scholar 

  • Takeda K., Takeuchi O. and Akira S. 2002 Recognition of lipopeptides by toll-like receptors. J. Endotoxin Res. 8, 459–463.

    Article  CAS  Google Scholar 

  • Taylor K. H., Taylor J. F., White S. N. and Womack J. E. 2006 Identification of genetic variation and putative regulatory regions in bovine CARD15. Mamm. Genome 17, 892–901.

    Article  CAS  Google Scholar 

  • Tewari D., Hovingh E., Linscott R., Martel E., Lawrence J., Wolfgang D. et al. 2014 Mycobacterium avium subsp. paratuberculosis antibody response, fecal shedding, and antibody cross-reactivity to Mycobacterium bovis in M. avium subsp. paratuberculosis-infected cattle herds vaccinated against Johne’s disease. Clin. Vaccine Immunol. 21, 698–703.

    Article  Google Scholar 

  • Trangoni M. D., Gioffré A. K., Cerón Cucchi M. E., Caimi K. C., Ruybal P., Zumárraga M. J. et al. 2015 LAMP technology: rapid identification of Brucella and Mycobacterium avium subsp. paratuberculosis. Braz. J. Microbiol. 46, 619–626.

  • Vordermeier M., Ameni G., Berg S., Bishop R., Robertson B. D., Aseffa A. et al. 2012 The influence of cattle breed on susceptibility to bovine tuberculosis in Ethiopia. Comp. Immunol. Microbiol. Infect. Dis. 35, 227–232.

    Article  Google Scholar 

  • Wentink G. H., Bongers J. H., Zeeuwen A. A. and Jaartsveld F. H. 1994 Incidence of paratuberculosis after vaccination against M. paratuberculosis in two infected dairy herds. Zentralbl. Vet. B 41, 517–522.

    CAS  Google Scholar 

  • Werling D., Jann O. C., Offord V., Glass E. J. and Coffey T. J. 2009 Variation matters: TLR structure and species-specific pathogen recognition. Trends Immunol. 30, 124–130.

    Article  CAS  Google Scholar 

  • White S. N., Taylor K. H., Abbey C. A., Gill C. A. and Womack J. E. 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.

    Article  CAS  Google Scholar 

  • Wiersinga W. J., Wieland C. W., Dessing M. C., Chantratita N., Cheng A. C., Limmathurotsakul D. et al. 2007 Toll-like receptor 2 impairs host defense in gram-negative sepsis caused by Burkholderia pseudomallei (Melioidosis). PLoS Med. 4, e248.

  • Yap G. S., Shaw M. H., Ling Y. and Sher A. 2006 Genetic analysis of host resistance to intracellular pathogens: lessons from studies of Toxoplasma gondii infection. Microbes Infect. 8, 1174–1188.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was financially supported by the Turkish Research Council (TUBITAK) grant number 115O478.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mehmet Ulas Cinar.

Additional information

Corresponding editor: Silvia Garagna

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (doc 89 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cinar, M.U., Hizlisoy, H., Akyüz, B. et al. Polymorphisms in toll-like receptor (TLR) 1, 4, 9 and SLC11A1 genes and their association with paratuberculosis susceptibility in Holstein and indigenous crossbred cattle in Turkey. J Genet 97, 1147–1154 (2018). https://doi.org/10.1007/s12041-018-1008-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12041-018-1008-7

Keywords

Navigation