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PloS one2014; 9(10); e109865; doi: 10.1371/journal.pone.0109865

Intramuscular administration of a synthetic CpG-oligodeoxynucleotide modulates functional responses of neutrophils of neonatal foals.

Abstract: Neutrophils play an important role in protecting against infection. Foals have age-dependent deficiencies in neutrophil function that may contribute to their predisposition to infection. Thus, we investigated the ability of a CpG-ODN formulated with Emulsigen to modulate functional responses of neutrophils in neonatal foals. Eighteen foals were randomly assigned to receive either a CpG-ODN with Emulsigen (N = 9) or saline intramuscularly at ages 1 and 7 days. At ages 1, 3, 9, 14, and 28, blood was collected and neutrophils were isolated from each foal. Neutrophils were assessed for basal and Rhodococcus equi-stimulated mRNA expression of the cytokines interferon-γ (IFN-γ), interleukin (IL)-4, IL-6, and IL-8 using real-time PCR, degranulation by quantifying the amount of β-D glucuronidase activity, and reactive oxygen species (ROS) generation using flow cytometry. In vivo administration of the CpG-ODN formulation on days 1 and 7 resulted in significantly (P<0.05) increased IFN-γ mRNA expression by foal neutrophils on days 3, 9, and 14. Degranulation was significantly (P<0.05) lower for foals in the CpG-ODN-treated group than the control group at days 3 and 14, but not at other days. No effect of treatment on ROS generation was detected. These results indicate that CpG-ODN administration to foals might improve innate and adaptive immune responses that could protect foals against infectious diseases and possibly improve responses to vaccination.
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Publication Date: 2014-10-15 PubMed ID: 25333660PubMed Central: PMC4198146DOI: 10.1371/journal.pone.0109865Google Scholar: Lookup
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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 research article discusses a study investigating the effect of a synthetic CpG-oligodeoxynucleotide (CpG-ODN) on the immune responses of newborn horses (foals). The researchers discovered that administering CpG-ODN enhanced the immune responses of the neutrophils in foals which could protect them from infectious diseases and improve responses to vaccination.

Research Context and Method

  • Neutrophils which are a type of white blood cell, play a vital role in the immune system’s mechanism for fighting off infections. This research explores a potential method for enhancing the functionality of these neutrophils in newborn horses, who often exhibit age-dependent deficiencies in their immune responses.
  • The researchers used a synthetic CpG-ODN in combination with Emulsigen, an adjuvant that enhances the body’s immune response, administered intramuscularly at two different stages of the foals’ early life – day one and day seven.
  • In order to evaluate the effects of the treatment, the researchers isolated neutrophils from blood samples taken from the foals at different ages post-treatment (day 1, 3, 9, 14, and 28). These neutrophils were then assessed for their functionality in various ways.

Findings and Results

  • Effects of the CpG-ODN treatments on the neutrophils’ functional responses were identified in a few key areas. Most prominently, it was found that interferon-γ (IFN-γ), a type of protein that helps stimulate the immune system, had significantly increased mRNA expression in treated foals.
  • These significant increases were observed on days 3, 9 and 14 post-treatment, indicating an enhanced immune response during these periods.
  • Additionally, degranulation, the process by which neutrophils release antimicrobial molecules, was significantly lower in treated foals compared to the control group on days 3 and 14. This suggests that CpG-ODN treatment possibly leads to a more controlled and efficient use of these cell resources.
  • However, the researchers did not observe any changes in the generation of reactive oxygen species (ROS), molecules that play a role in cell signaling and homeostasis.

Implications of the Research

  • The findings present potential for using CpG-ODN treatment to augment immune responses in newborn horses, which could offer better protection against infectious diseases.
  • Additionally, it may also improve responses to vaccination, thus broadening the implications beyond natural disease resistance.

Cite This Article

APA
Cohen ND, Bourquin JR, Bordin AI, Kuskie KR, Brake CN, Weaver KB, Liu M, Felippe MJ, Kogut MH. (2014). Intramuscular administration of a synthetic CpG-oligodeoxynucleotide modulates functional responses of neutrophils of neonatal foals. PLoS One, 9(10), e109865. https://doi.org/10.1371/journal.pone.0109865

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 9
Issue: 10
Pages: e109865
PII: e109865

Researcher Affiliations

Cohen, Noah D
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Bourquin, Jessica R
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Bordin, Angela I
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Kuskie, Kyle R
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Brake, Courtney N
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Weaver, Kaytee B
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Liu, Mei
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America.
Felippe, M Julia B
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Kogut, Michael H
  • Food and Feed Safety Research, Agricultural Research Service, Southern Plains Agricultural Research Center, USDA, College Station, Texas, United States of America.

MeSH Terms

  • Animals
  • Animals, Newborn
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Gene Expression Regulation / drug effects
  • Horses
  • Injections, Intramuscular
  • Male
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Oligodeoxyribonucleotides / administration & dosage
  • Reactive Oxygen Species / metabolism

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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Citations

This article has been cited 8 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.
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  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.
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  3. 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.
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  7. da Silveira BP, Kahn SK, Legere RM, Bray JM, Cole-Pfeiffer HM, Golding MC, Cohen ND, Bordin AI. Enteral immunization with live bacteria reprograms innate immune cells and protects neonatal foals from pneumonia. Sci Rep 2025 May 25;15(1):18156.
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  8. 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.
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