Activation of foal neutrophils at different ages by CpG oligodeoxynucleotides and Rhodococcus equi.
Abstract: Toll-like receptor 9 (TLR9) activation stimulates protective immune responses against intracellular pathogens by phagocytes, including neutrophils. This study examined TLR9-mediated neutrophil activation in neonatal foals. Unmethylated CpGs, ligands for TLR9, were used to stimulate equine neutrophils, either purified or in contact with other peripheral blood leukocytes. Rhodococcus equi was used as another stimulus in parallel. TLR9 mRNA was constitutively expressed at a similar level in purified equine neutrophils across different ages from birth to adulthood, and expression was not affected by either CpG or R. equi. Purified foal neutrophils were directly sensitive to CpG stimulation, reflected by enhanced reactive oxygen species generation following fMLP stimulation, and by expressing significantly (P<0.05) greater mRNA of IFN-gamma, IL-8, IL-12p35, and significantly (P<0.05) decreased TNF-alpha mRNA. In comparison, purified foal neutrophils stimulated by R. equi showed significantly (P<0.05) increased mRNA production of IL-6, IL-8, IL-23p19, and TNF-alpha. Neutrophils co-cultured with other leukocytes expressed a distinct profile of cytokine mRNA than purified neutrophils in response to CpG stimulation, whereas the profile was very similar following R. equi stimulation irrespective of neutrophil purity. When co-cultured with other leukocytes, foal neutrophils were significantly (P<0.05) activated at birth by B-class CpGs and produced IL-6, IL-8, IL-12p40, and IL-23p19 at similar magnitudes to those at 2 months of age. In foal neutrophils at birth, R. equi significantly (P<0.05) induced all cytokines stimulated by CpGs (except IL-12p40), as well as TNF-alpha. Our results indicate that foal neutrophils were sensitive to CpG or R. equi activation as early as at birth, and that B-class CpGs enhanced foal neutrophil functions in vitro.
Publication Date: 2009-10-09 PubMed ID: 19819162DOI: 10.1016/j.cyto.2009.08.012Google 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.
- 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.
The research investigates the impact of Toll-like receptor 9 (TLR9) activation on stimulating immune responses in newborn horses (foals). The study found that foal neutrophils, which help defend against pathogens, responded to stimulus from TLR9 ligands and the bacteria Rhodococcus equi starting from birth.
Activation of Foal Neutrophils
- In this study, the team focused on the early immune system development in newborn horses (foals), specifically the activation of a type of white blood cell called neutrophils.
- The researchers used Toll-like receptor 9 (TLR9) and Rhodococcus equi, a bacterium responsible for a common disease in foals, to activate the neutrophils.
- Neutrophils are a type of phagocyte, a cell capable of engulfing and absorbing bacteria and other small cells and particles. They play a crucial role in the immune system.
Observations across Different Ages
- Researchers found that TLR9 was expressed similarly in purified neutrophils across various ages, from birth to adulthood, and that this expression wasn’t significantly affected by exposure to TLR9 ligands (unmethylated CpGs) or R. equi.
- The team assessed the impact of these stimuli on neutrophils’ reactivity, cytokine production (immunoregulatory substances), and their capacity to generate reactive oxygen species, which are involved in destroying foreign substances in the body.
- It was observed that the neutrophils of foals showed increased reactivity and altered cytokine production both when subjected to TLR9 ligands and when exposed to R. equi.
Neutrophils Response to Stimulation
- The study also found that co-culturing neutrophils with other white blood cells affected their response to TLR9 ligands but not to R. equi.
- In response to TLR9 ligands, neutrophils produced different cytokine profiles when co-cultured with other leukocytes compared to when they were isolated and purified. However, their response to R. equi remained consistent.
- Importantly, the results demonstrated that foal neutrophils could be activated by TLR9 ligands and R. equi as early as at birth. This is crucial information for understanding the early development of the neonatal immune system in horses and can potentially inform strategies to support foals’ health.
Cite This Article
APA
Liu M, Liu T, Bordin A, Nerren J, Cohen N.
(2009).
Activation of foal neutrophils at different ages by CpG oligodeoxynucleotides and Rhodococcus equi.
Cytokine, 48(3), 280-289.
https://doi.org/10.1016/j.cyto.2009.08.012 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843-4475, USA.
MeSH Terms
- Age Factors
- Animals
- Animals, Newborn
- Cells, Cultured
- Gene Expression Regulation / drug effects
- Horses
- Interferon-gamma / metabolism
- Neutrophils / drug effects
- Neutrophils / microbiology
- Oligodeoxyribonucleotides / metabolism
- Oligodeoxyribonucleotides / pharmacology
- RNA, Messenger / metabolism
- Rhodococcus equi / immunology
- Toll-Like Receptor 9 / genetics
- Toll-Like Receptor 9 / metabolism
- Tumor Necrosis Factor-alpha / metabolism
Citations
This article has been cited 9 times.- 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.
- 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.
- De Dios R, Nguyen L, Ghosh S, McKenna S, Wright CJ. CpG-ODN-mediated TLR9 innate immune signalling and calcium dyshomeostasis converge on the NFκB inhibitory protein IκBβ to drive IL1α and IL1β expression. Immunology 2020 May;160(1):64-77.
- 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.
- 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.
- 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.
- 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.
- Werners AH, Bryant CE. Pattern recognition receptors in equine endotoxaemia and sepsis. Equine Vet J 2012 Jul;44(4):490-8.
- 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.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
