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Veterinary immunology and immunopathology2011; 145(1-2); 290-297; doi: 10.1016/j.vetimm.2011.11.012

Neutrophil function of neonatal foals is enhanced in vitro by CpG oligodeoxynucleotide stimulation.

Abstract: Rhodococcus equi is an intracellular bacterium that causes pneumonia in foals and immunocompromised adult horses. Evidence exists that foals become infected with R. equi early in life, a period when innate immune responses are critically important for protection against infection. Neutrophils are innate immune cells that play a key role in defense against this bacterium. Enhancing neutrophil function during early life could thus help to protect foals against R. equi infection. The objective of our study was to determine whether in vitro incubation with the TLR9 agonist CpG 2142 would enhance degranulation and gene expression of cytokines and Toll-like receptor 9 (TLR9) by neutrophils collected from foals at 2, 14, and 56 days of life, and to determine whether these stimulated responses varied among ages. Neutrophil degranulation was enhanced at all ages by in vitro stimulation with either CpG alone, R. equi alone, or in combination with either R. equi or N-formyl-methionyl-leucyl-phenylalanine (fMLP) (P<0.05), but not by in vitro stimulation with fMLP alone. There were no significant differences among ages in CpG-induced cytokine expression, except for IL-12p40, which was induced more at 56 days of age than on days 2 or 14. Collapsing data across ages, CpG 2142 significantly (P<0.05) increased IL-6 and IL-17 mRNA expression. We concluded that in vitro stimulation of foal neutrophils with CpG enhances their function by promoting degranulation and inducing mRNA expression of IL-6 and IL-17, regardless of age.
Publication Date: 2011-11-25 PubMed ID: 22197007DOI: 10.1016/j.vetimm.2011.11.012Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

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The research article investigates if stimulating neutrophils, a type of innate immune cell, from young horses (foals) with a TLR9 agonist called CpG 2142 increases their ability to fight Rhodococcus equi, a bacterium that causes pneumonia in horses. The research also studies if this stimulation is effective at different stages of a foal’s life.

Objective and Method of Study

  • The aim of the study was to verify whether the neutrophils from neonatal foals would respond favorably to in vitro stimulation with the TLR9 agonist CpG 2142 and how it would affect their function at varying ages (2, 14, and 56 days) to fight against Rhodococcus equi infection.
  • In the experiment, researchers examined the degranulation (a process where cells release antimicrobial cytotoxic molecules) and gene expressions of cytokines and TLR9 (part of the immune system that recognizes foreign substances) in neutrophils after treatment with CpG 2142.

Results and Findings

  • According to the findings, neutrophil degranulation was notably enhanced when stimulated with CpG alone, R. equi alone or in combination with either R. equi or another compound, N-formyl-methionyl-leucyl-phenylalanine (fMLP). However, this enhancement was not observed when neutrophils were stimulated with fMLP alone.
  • There weren’t significant differences in CpG-induced cytokine expression across different ages. However, more expression of IL-12p40 cytokine was observed on day 56 as compared to days 2 or 14.
  • When the data were compiled across all ages, it was observed that CpG 2142 significantly increased the mRNA expression of cytokines IL-6 and IL-17.

Conclusion

  • From the experiment, the researchers concluded that in vitro stimulation of neutrophils from foals with CpG 2142 enhances their function by promoting degranulation and inducing mRNA expression of cytokines IL-6 and IL-17, and this holds true regardless of the age of the foal.
  • This could mean that CpG 2142 can be used to bolster the immune response in foals against Rhodococcus equi infection, potentially reducing the incidence of pneumonia in young horses.

Cite This Article

APA
Bordin AI, Liu M, Nerren JR, Buntain SL, Brake CN, Kogut MH, Cohen ND. (2011). Neutrophil function of neonatal foals is enhanced in vitro by CpG oligodeoxynucleotide stimulation. Vet Immunol Immunopathol, 145(1-2), 290-297. https://doi.org/10.1016/j.vetimm.2011.11.012

Publication

ISSN: 1873-2534
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 145
Issue: 1-2
Pages: 290-297

Researcher Affiliations

Bordin, Angela I
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4475, USA.
Liu, Mei
    Nerren, Jessica R
      Buntain, Stephanie L
        Brake, Courtney N
          Kogut, Michael H
            Cohen, Noah D

              MeSH Terms

              • Actinomycetales Infections / immunology
              • Actinomycetales Infections / prevention & control
              • Actinomycetales Infections / veterinary
              • Animals
              • Animals, Newborn / immunology
              • Cytokines / biosynthesis
              • Drug Therapy, Combination
              • Horse Diseases / immunology
              • Horse Diseases / prevention & control
              • Horses / immunology
              • Immunity, Innate / drug effects
              • Immunity, Innate / immunology
              • Interleukin-17 / biosynthesis
              • Interleukin-6 / biosynthesis
              • N-Formylmethionine Leucyl-Phenylalanine / administration & dosage
              • N-Formylmethionine Leucyl-Phenylalanine / therapeutic use
              • Neutrophils / drug effects
              • Neutrophils / immunology
              • Oligodeoxyribonucleotides / administration & dosage
              • Oligodeoxyribonucleotides / therapeutic use
              • Rhodococcus equi / immunology
              • Toll-Like Receptor 9 / biosynthesis

              Citations

              This article has been cited 11 times.
              1. Cohen ND, Kahn SK, Cywes-Bentley C, Ramirez-Cortez S, Schuckert AE, Vinacur M, Bordin AI, Pier GB. Serum Antibody Activity against Poly-N-Acetyl Glucosamine (PNAG), but Not PNAG Vaccination Status, Is Associated with Protecting Newborn Foals against Intrabronchial Infection with Rhodococcus equi. Microbiol Spectr 2021 Sep 3;9(1):e0063821.
                doi: 10.1128/Spectrum.00638-21pubmed: 34319137google scholar: lookup
              2. Bordin AI, Cohen ND, Giguère S, Bray JM, Berghaus LJ, Scott B, Johnson R, Hook M. Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia. Sci Rep 2021 Jan 28;11(1):2483.
                doi: 10.1038/s41598-021-82049-ypubmed: 33510265google scholar: lookup
              3. Zhang J, Fu B, Lin Q, Riley IT, Ding S, Chen L, Cui J, Yang L, Li H. Colonization of Beauveria bassiana 08F04 in root-zone soil and its biocontrol of cereal cyst nematode (Heterodera filipjevi). PLoS One 2020;15(5):e0232770.
                doi: 10.1371/journal.pone.0232770pubmed: 32369513google scholar: lookup
              4. Folmar CN, Cywes-Bentley C, Bordin AI, Rocha JN, Bray JM, Kahn SK, Schuckert AE, Pier GB, Cohen ND. In vitro evaluation of complement deposition and opsonophagocytic killing of Rhodococcus equi mediated by poly-N-acetyl glucosamine hyperimmune plasma compared to commercial plasma products. J Vet Intern Med 2019 May;33(3):1493-1499.
                doi: 10.1111/jvim.15511pubmed: 31034109google scholar: lookup
              5. Rocha JN, Cohen ND, Bordin AI, Brake CN, Giguère S, Coleman MC, Alaniz RC, Lawhon SD, Mwangi W, Pillai SD. Oral Administration of Electron-Beam Inactivated Rhodococcus equi Failed to Protect Foals against Intrabronchial Infection with Live, Virulent R. equi. PLoS One 2016;11(2):e0148111.
                doi: 10.1371/journal.pone.0148111pubmed: 26828865google scholar: lookup
              6. Schnabel CL, Steinig P, Koy M, Schuberth HJ, Juhls C, Oswald D, Wittig B, Willenbrock S, Murua Escobar H, Pfarrer C, Wagner B, Jaehnig P, Moritz A, Feige K, Cavalleri JM. Immune response of healthy horses to DNA constructs formulated with a cationic lipid transfection reagent. BMC Vet Res 2015 Jun 23;11:140.
                doi: 10.1186/s12917-015-0452-3pubmed: 26100265google scholar: lookup
              7. Cohen ND, Bourquin JR, Bordin AI, Kuskie KR, Brake CN, Weaver KB, Liu M, Felippe MJ, Kogut MH. Intramuscular administration of a synthetic CpG-oligodeoxynucleotide modulates functional responses of neutrophils of neonatal foals. PLoS One 2014;9(10):e109865.
                doi: 10.1371/journal.pone.0109865pubmed: 25333660google scholar: lookup
              8. McQueen CM, Doan R, Dindot SV, Bourquin JR, Zlatev ZZ, Chaffin MK, Blodgett GP, Ivanov I, Cohen ND. Identification of genomic loci associated with Rhodococcus equi susceptibility in foals. PLoS One 2014;9(6):e98710.
                doi: 10.1371/journal.pone.0098710pubmed: 24892408google scholar: lookup
              9. Lohmann KL, Lopez AM, Manning ST, Marques FJ, Brownlie R, Allen AL, Sangster AE, Mutwiri G, Gerdts V, Potter A, Townsend HG. Failure of a VapA/CpG oligodeoxynucleotide vaccine to protect foals against experimental Rhocococcus equi pneumonia despite induction of VapA-specific antibody and interferon-γ response. Can J Vet Res 2013 Jul;77(3):161-9.
                pubmed: 24101791
              10. Kachroo P, Ivanov I, Seabury AG, Liu M, Chowdhary BP, Cohen ND. Age-related changes following in vitro stimulation with Rhodococcus equi of peripheral blood leukocytes from neonatal foals. PLoS One 2013;8(5):e62879.
                doi: 10.1371/journal.pone.0062879pubmed: 23690962google scholar: lookup
              11. da Silveira BP, Cohen ND, Lawhon SD, Watson RO, Bordin AI. Protective immune response against Rhodococcus equi: An innate immunity-focused review. Equine Vet J 2025 May;57(3):563-586.
                doi: 10.1111/evj.14214pubmed: 39258739google scholar: lookup