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

PLoS One. 2014 Oct 15;9(10):e109865. doi: 10.1371/journal.pone.0109865. eCollection 2014.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

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

Substances

  • CPG-oligonucleotide
  • Cytokines
  • Oligodeoxyribonucleotides
  • Reactive Oxygen Species

Grants and funding

This work was supported by a grant from the USDA-CSREES (TEX018399), with additional support from the Link Equine Research Endowment, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Dr. Bordin was supported by a fellowship from Fort Dodge Animal Health/Pfizer Animal Health (now Zoetis). The corporate support for Dr. Bordin's scholarship had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The CpG-ODN used in this study was provided by Merial, Ltd. Merial had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.