Postnatal changes in epigenetic modifications of neutrophils of foals are associated with increased ROS function and regulation of neutrophil function.
Abstract: Neonates of all species, including foals, are highly susceptible to infection, and neutrophils play a crucial role in innate immunity to infection. Evidence exists that neutrophils of neonatal foals are functionally deficient during the first weeks of life, including expression of cytokine genes such as IFNG. We hypothesized that postnatal epigenetic changes were likely to regulate the observed age-related changes in foal neutrophils. Using ChIP-Seq, we identified significant differences in trimethylated histone H3 lysine 4, an epigenetic modification associated with active promoters and enhancers, in neutrophils in foals at 30 days of age relative to 1 day of age. These chromatin changes were associated with genes implicated in immune responses and were consistent with age-related changes in neutrophil functional responses including ROS generation and IFN expression. Postnatal changes in epigenetic modifications suggest that environmentally-mediated cues help to promote maturation of neutrophil functional responses. Elucidating the environmental triggers and their signaling pathways could provide a means for improving innate immune responses of neonates to improve their ability to combat infectious diseases.
Copyright © 2018 Elsevier Ltd. All rights reserved.
Publication Date: 2018-06-26 PubMed ID: 29958850DOI: 10.1016/j.dci.2018.06.012Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research explores how changes in the epigenetic modifications of neutrophils in foals after birth lead to improved resistance to infections. The study argues that environmentally-mediated cues contribute to the development of the functionality of the neutrophils.
Background
- The study starts from an already established premise that newborns, inclusive of colts, are extremely susceptible to infections due to an innate immunity that is considerably weak.
- The paper acknowledges the crucial role that neutrophils play in the initial defense against infections.
- There is existing research indicating that neonatal foals’ neutrophils are functionally compromised during their initial weeks of life, affecting the expression of certain vital cytokine genes like IFNG.
Hypothesis
- Based on these facts, the researchers hypothesized that the age-related changes witnessed in foal neutrophils could be as a result of postnatal epigenetic changes.
Method and Data Collection
- To test their hypothesis, the researchers used ChIP-Seq, an approach used to analyze how proteins interact with DNA, to identify any significant variances in the trimethylated histone H3 lysine 4 in the foal’s neutrophils.
- The trimethylated histone H3 lysine 4 is an epigenetic modification coupled with active promoters and enhancers.
- The observed differences were between neutrophils in foals at one day old and those at 30 days old.
Findings
- The results showed that these chromatin changes were consistent with genes involved in immune responses.
- More significantly, these changes were aligned with age-related changes in the functional responses of neutrophils, including ROS generation and IFN expression.
Conclusions
- The study found out that postnatal changes in epigenetic modifications play a key role in suggesting that environmentally-mediated signals assist in the maturation of the functional responses of neutrophils.
- A proper understanding of these environmental triggers and the pathways they signal could be instrumental in improving the innate immune responses of newborns, enhancing their ability to fight against infectious diseases.
Cite This Article
APA
Dindot SV, Doan RN, Kuskie KR, Hillman PR, Whitfield CM, McQueen CM, Bordin AI, Bourquin JR, Cohen ND.
(2018).
Postnatal changes in epigenetic modifications of neutrophils of foals are associated with increased ROS function and regulation of neutrophil function.
Dev Comp Immunol, 87, 182-187.
https://doi.org/10.1016/j.dci.2018.06.012 Publication
Researcher Affiliations
- Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA; Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, TX, USA. Electronic address: sdindot@cvm.tamu.edu.
- Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA.
- Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA.
- Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, TX, USA.
- Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA.
- Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA.
- Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA.
- Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA.
- Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA. Electronic address: ncohen@cvm.tamu.edu.
MeSH Terms
- Animals
- Animals, Newborn
- Cytokines / genetics
- Cytokines / immunology
- Epigenesis, Genetic
- Histones / metabolism
- Horse Diseases / genetics
- Horse Diseases / immunology
- Horses / genetics
- Horses / growth & development
- Horses / metabolism
- Immunity, Innate / genetics
- Immunity, Innate / immunology
- Lysine / metabolism
- Methylation
- Neutrophils / immunology
- Neutrophils / metabolism
- Promoter Regions, Genetic / genetics
- Reactive Oxygen Species / metabolism
- Signal Transduction / genetics
- Signal Transduction / immunology
Citations
This article has been cited 6 times.- Bermick J, Schaller M. Epigenetic regulation of pediatric and neonatal immune responses. Pediatr Res 2022 Jan;91(2):297-327.
- Wang R, Han ZJ, Song G, Cui Y, Xia HF, Ma X. Homocysteine-induced neural tube defects in chick embryos via oxidative stress and DNA methylation associated transcriptional down-regulation of miR-124. Toxicol Res (Camb) 2021 May;10(3):425-435.
- 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.
- Villalba-Orero M, Gómez CA, Valero-Gónzalez M, Venegas N, Criado G, Martín-Cuervo M. Blood parameters in neonatal foal and colostrum quality as possible early markers for increased risk of developing Rhodococcus equi pneumonia. Front Vet Sci 2025;12:1654052.
- 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.
- 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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