FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / PLoS One / Effects of Separate and Concomitant TLR-2 and TLR-4 Activati...
PloS one2013; 8(6); e66897; doi: 10.1371/journal.pone.0066897

Effects of Separate and Concomitant TLR-2 and TLR-4 Activation in Peripheral Blood Mononuclear Cells of Newborn and Adult Horses.

Abstract: Deficient innate and adaptive immune responses cause newborn mammals to be more susceptible to bacterial infections than adult individuals. Toll-like receptors (TLRs) are known to play a pivotal role in bacterial recognition and subsequent immune responses. Several studies have indicated that activation of certain TLRs, in particular TLR-2, can result in suppression of inflammatory pathology. In this study, we isolated peripheral blood mononuclear cells (PBMCs) from adult and newborn horses to investigate the influence of TLR-2 activation on the inflammatory response mediated by TLR-4. Data were analysed in a Bayesian hierarchical linear regression model, accounting for variation between horses. In general, cytokine responses were lower in PBMCs derived from foals compared with PBMCs from adult horses. Whereas in foal PBMCs expression of TLR-2, TLR-4, and TLR-9 was not influenced by separate and concomitant TLR-2 and TLR-4 activation, in adult horse PBMCs, both TLR ligands caused significant up-regulation of TLR-2 and down-regulation of TLR-9. Moreover, in adult horse PBMCs, interleukin-10 protein production and mRNA expression increased significantly following concomitant TLR-2 and TLR-4 activation (compared with sole TLR-4 activation). In foal PBMCs, this effect was not observed. In both adult and foal PBMCs, the lipopolysaccharide-induced pro-inflammatory response was not influenced by pre-incubation and co-stimulation with the specific TLR-2 ligand Pam3-Cys-Ser-Lys4. This indicates that the published data on other species cannot be translated directly to the horse, and stresses the necessity to confirm results obtained in other species in target animals. Future research should aim to identify other methods or substances that enhance TLR functionality and bacterial defence in foals, thereby lowering susceptibility to life-threatening infections during the first period of life.
Get Full Text
Publication Date: 2013-06-19 PubMed ID: 23840549PubMed Central: PMC3686748DOI: 10.1371/journal.pone.0066897Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explores the impact of activating certain immune system receptors (TLR-2 and TLR-4) in both newborn and adult horses. It found differences in how the immune systems of these two age groups responded, with adult horses experiencing notable changes in immune system functionality that were not present in newborns.

Research Background

  • It’s known that newborn mammals often have weaker immune responses than adults, which leaves them more vulnerable to bacterial infections.
  • The study focuses on Toll-like Receptors (TLRs), which are crucial in recognizing bacterial threats and initiating immune responses.
  • Prior research has suggested that certain TLRs, specifically TLR-2, can help suppress inflammatory diseases when activated.

Research Methodology

  • Researchers collected Peripheral Blood Mononuclear Cells (PBMCs) from both adult and newborn horses.
  • They then examined the effects of activating TLR-2 in relation to the inflammatory response mediated by TLR-4.
  • Considering variations between different horses, data were analysed in a Bayesian hierarchical linear regression model.

Findings

  • The investigated immune responses were weaker in foal-derived PBMCs compared to the ones from adult horses.
  • It was observed that the expression of TLR-2, TLR-4, and TLR-9 in foal PBMCs did not change with separate or combined TLR-2 and TLR-4 activation.
  • In adult horse PBMCs, however, both TLR ligands caused significant up-regulation of TLR-2 and down-regulation of TLR-9.
  • Furthermore, in adult horse PBMCs, the production and expression of a key immune regulator, interleukin-10, significantly increased when both TLR-2 and TLR-4 were activated together (compared to only activating TLR-4).
  • Such an effect was not observed in foal PBMCs. Also, neither foal nor adult PBMCs showed any change in their response to a pro-inflammatory trigger when pre-incubated with a specific TLR-2 ligand.

Implications and Future Research

  • The results demonstrated a significant difference between the immune cell responses of newborn and adult horses.
  • This points to the need for species-specific and age-specific research in immune functionality.
  • Future research should explore ways to enhance TLR functionality and improve the bacterial defense system in newborn horses to potentially reduce their infection susceptibility.

Cite This Article

APA
Vendrig JC, Coffeng LE, Fink-Gremmels J. (2013). Effects of Separate and Concomitant TLR-2 and TLR-4 Activation in Peripheral Blood Mononuclear Cells of Newborn and Adult Horses. PLoS One, 8(6), e66897. https://doi.org/10.1371/journal.pone.0066897

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 8
Issue: 6
Pages: e66897
PII: e66897

Researcher Affiliations

Vendrig, Johannes Cornelis
  • Veterinary Pharmacology, Pharmacotherapy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Coffeng, Luc Edgar
    Fink-Gremmels, Johanna

      MeSH Terms

      • Animals
      • Animals, Newborn
      • Bayes Theorem
      • Cells, Cultured
      • Female
      • Gene Expression Regulation / drug effects
      • Horses / immunology
      • Interleukin-10 / genetics
      • Interleukin-10 / metabolism
      • Leukocytes, Mononuclear / cytology
      • Leukocytes, Mononuclear / drug effects
      • Leukocytes, Mononuclear / immunology
      • Ligands
      • Lipopolysaccharides / pharmacology
      • Male
      • Toll-Like Receptor 2 / genetics
      • Toll-Like Receptor 2 / metabolism
      • Toll-Like Receptor 4 / genetics
      • Toll-Like Receptor 4 / metabolism

      Conflict of Interest Statement

      The authors have the following interests. The senior author is editor in chief with the ‘Journal of Veterinary Pharmacology and Therapeutics. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

      References

      This article includes 31 references
      1. Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates.. Nat Rev Immunol 2007 May;7(5):379-90.
        pubmed: 17457344doi: 10.1038/nri2075google scholar: lookup
      2. Adkins B, Leclerc C, Marshall-Clarke S. Neonatal adaptive immunity comes of age.. Nat Rev Immunol 2004 Jul;4(7):553-64.
        pubmed: 15229474doi: 10.1038/nri1394google scholar: lookup
      3. Liu T, Nerren J, Liu M, Martens R, Cohen N. Basal and stimulus-induced cytokine expression is selectively impaired in peripheral blood mononuclear cells of newborn foals.. Vaccine 2009 Jan 29;27(5):674-83.
        pubmed: 19056444doi: 10.1016/j.vaccine.2008.11.040google scholar: lookup
      4. Mérant C, Breathnach CC, Kohler K, Rashid C, Van Meter P, Horohov DW. Young foal and adult horse monocyte-derived dendritic cells differ by their degree of phenotypic maturity.. Vet Immunol Immunopathol 2009 Sep 15;131(1-2):1-8.
        pubmed: 19349079doi: 10.1016/j.vetimm.2009.03.002google scholar: lookup
      5. Breathnach CC, Sturgill-Wright T, Stiltner JL, Adams AA, Lunn DP, Horohov DW. Foals are interferon gamma-deficient at birth.. Vet Immunol Immunopathol 2006 Aug 15;112(3-4):199-209.
        pubmed: 16621024doi: 10.1016/j.vetimm.2006.02.010google scholar: lookup
      6. Liu M, Bordin A, Liu T, Russell K, Cohen N. Gene expression of innate Th1-, Th2-, and Th17-type cytokines during early life of neonatal foals in response to Rhodococcus equi.. Cytokine 2011 Nov;56(2):356-64.
        pubmed: 21835631doi: 10.1016/j.cyto.2011.07.017google scholar: lookup
      7. Jacks S, Giguère S, Crawford PC, Castleman WL. Experimental infection of neonatal foals with Rhodococcus equi triggers adult-like gamma interferon induction.. Clin Vaccine Immunol 2007 Jun;14(6):669-77.
        pmc: PMC1951072pubmed: 17409222doi: 10.1128/cvi.00042-07google scholar: lookup
      8. Takeuchi O, Akira S. Pattern recognition receptors and inflammation.. Cell 2010 Mar 19;140(6):805-20.
        pubmed: 20303872doi: 10.1016/j.cell.2010.01.022google scholar: lookup
      9. Testro AG, Visvanathan K. Toll-like receptors and their role in gastrointestinal disease.. J Gastroenterol Hepatol 2009 Jun;24(6):943-54.
        pubmed: 19638078doi: 10.1111/j.1440-1746.2009.05854.xgoogle scholar: lookup
      10. Abdelsadik A, Trad A. Toll-like receptors on the fork roads between innate and adaptive immunity.. Hum Immunol 2011 Dec;72(12):1188-93.
        pubmed: 21920397doi: 10.1016/j.humimm.2011.08.015google scholar: lookup
      11. Buwitt-Beckmann U, Heine H, Wiesmüller KH, Jung G, Brock R, Akira S, Ulmer AJ. TLR1- and TLR6-independent recognition of bacterial lipopeptides.. J Biol Chem 2006 Apr 7;281(14):9049-57.
        pubmed: 16455646doi: 10.1074/jbc.m512525200google scholar: lookup
      12. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5.. Nature 2001 Apr 26;410(6832):1099-103.
        pubmed: 11323673doi: 10.1038/35074106google scholar: lookup
      13. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S. A Toll-like receptor recognizes bacterial DNA.. Nature 2000 Dec 7;408(6813):740-5.
        pubmed: 11130078doi: 10.1038/35047123google scholar: lookup
      14. Bernheiden M, Heinrich JM, Minigo G, Schütt C, Stelter F, Freeman M, Golenbock D, Jack RS. LBP, CD14, TLR4 and the murine innate immune response to a peritoneal Salmonella infection.. J Endotoxin Res 2001;7(6):447-50.
        pubmed: 11753215
      15. Takeuchi O, Hoshino K, Akira S. Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection.. J Immunol 2000 Nov 15;165(10):5392-6.
        pubmed: 11067888doi: 10.4049/jimmunol.165.10.5392google scholar: lookup
      16. Cario E, Gerken G, Podolsky DK. Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function.. Gastroenterology 2007 Apr;132(4):1359-74.
        pubmed: 17408640doi: 10.1053/j.gastro.2007.02.056google scholar: lookup
      17. Cario E, Gerken G, Podolsky DK. Toll-like receptor 2 enhances ZO-1-associated intestinal epithelial barrier integrity via protein kinase C.. Gastroenterology 2004 Jul;127(1):224-38.
        pubmed: 15236188doi: 10.1053/j.gastro.2004.04.015google scholar: lookup
      18. Re F, Strominger JL. IL-10 released by concomitant TLR2 stimulation blocks the induction of a subset of Th1 cytokines that are specifically induced by TLR4 or TLR3 in human dendritic cells.. J Immunol 2004 Dec 15;173(12):7548-55.
        pubmed: 15585882doi: 10.4049/jimmunol.173.12.7548google scholar: lookup
      19. Flaminio MJ, Borges AS, Nydam DV, Horohov DW, Hecker R, Matychak MB. The effect of CpG-ODN on antigen presenting cells of the foal.. J Immune Based Ther Vaccines 2007 Jan 25;5:1.
        pmc: PMC1797044pubmed: 17254326doi: 10.1186/1476-8518-5-1google scholar: lookup
      20. Plummer M (2012) http://mcmc-jags.sourceforge.net.
      21. R Development Core Team. R: A language and environment for statistical computing.. Vienna, Austria: R Foundation for Statistical Computing.
      22. Plummer M (2011) http://CRAN.R-project.org/package=rjags.
      23. Su Y (2011) http://CRAN.R-project.org/package=R2jags.
      24. Gelman A, Rubin DB. Inference from iterative simulation using multiple sequences.. Statistical Science 7: 457–511.
      25. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.. Methods 2001 Dec;25(4):402-8.
        pubmed: 11846609doi: 10.1006/meth.2001.1262google scholar: lookup
      26. Borchers AT, Selmi C, Meyers FJ, Keen CL, Gershwin ME. Probiotics and immunity.. J Gastroenterol 2009;44(1):26-46.
        pubmed: 19159071doi: 10.1007/s00535-008-2296-0google scholar: lookup
      27. Nyirenda MH, O'Brien K, Sanvito L, Constantinescu CS, Gran B. Modulation of regulatory T cells in health and disease: role of toll-like receptors.. Inflamm Allergy Drug Targets 2009 Jun;8(2):124-9.
        pubmed: 19530994doi: 10.2174/187152809788462581google scholar: lookup
      28. Figueiredo MD, Vandenplas ML, Hurley DJ, Moore JN. Differential induction of MyD88- and TRIF-dependent pathways in equine monocytes by Toll-like receptor agonists.. Vet Immunol Immunopathol 2009 Jan 15;127(1-2):125-34.
        pubmed: 19019456doi: 10.1016/j.vetimm.2008.09.028google scholar: lookup
      29. Dowling D, Hamilton CM, O'Neill SM. A comparative analysis of cytokine responses, cell surface marker expression and MAPKs in DCs matured with LPS compared with a panel of TLR ligands.. Cytokine 2008 Mar;41(3):254-62.
        pubmed: 18221884doi: 10.1016/j.cyto.2007.11.020google scholar: lookup
      30. Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB, Schroeder L, Aderem A. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors.. Proc Natl Acad Sci U S A 2000 Dec 5;97(25):13766-71.
        pmc: PMC17650pubmed: 11095740doi: 10.1073/pnas.250476497google scholar: lookup
      31. Long EM, Millen B, Kubes P, Robbins SM. Lipoteichoic acid induces unique inflammatory responses when compared to other toll-like receptor 2 ligands.. PLoS One 2009;4(5):e5601.
        pmc: PMC2680621pubmed: 19440307doi: 10.1371/journal.pone.0005601google scholar: lookup

      Citations

      This article has been cited 5 times.
      1. Wang J, Li R, Zhang M, Gu C, Wang H, Feng J, Bao L, Wu Y, Chen S, Zhang X. Influence of Huangqin Decoction on the immune function and fecal microbiome of chicks after experimental infection with Escherichia coli O78.. Sci Rep 2022 Oct 5;12(1):16632.
        doi: 10.1038/s41598-022-20709-3pubmed: 36198724google scholar: lookup
      2. Anna M, Łukasz M, Adam O, Chełmońska-Soyta A. Effectiveness of immunization with multi-component bacterial immunomodulator in foals at 35th day of life.. Sci Rep 2022 Sep 22;12(1):15795.
        doi: 10.1038/s41598-022-17532-1pubmed: 36138050google scholar: lookup
      3. Migdał A, Migdał Ł, Oczkowicz M, Okólski A, Chełmońska-Soyta A. Influence of Age and Immunostimulation on the Level of Toll-Like Receptor Gene (TLR3, 4, and 7) Expression in Foals.. Animals (Basel) 2020 Oct 26;10(11).
        doi: 10.3390/ani10111966pubmed: 33114637google scholar: lookup
      4. Tallmadge RL, Wang M, Sun Q, Felippe MJB. Transcriptome analysis of immune genes in peripheral blood mononuclear cells of young foals and adult horses.. PLoS One 2018;13(9):e0202646.
        doi: 10.1371/journal.pone.0202646pubmed: 30183726google scholar: lookup
      5. Basto AP, Leitão A. Targeting TLR2 for vaccine development.. J Immunol Res 2014;2014:619410.
        doi: 10.1155/2014/619410pubmed: 25057505google scholar: lookup
      Subscribe to our newsletter
      Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.