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Veterinary immunology and immunopathology2008; 127(3-4); 212-219; doi: 10.1016/j.vetimm.2008.10.004

Age-related changes in cytokine expression by neutrophils of foals stimulated with virulent Rhodococcus equi in vitro.

Abstract: Although evidence exists that neutrophils play a vital role in resistance to infection with Rhodococcus equi, the means by which neutrophils exert their effects have not been clearly defined. In the present study we evaluated differences in cytokine expression by unstimulated and R. equi-stimulated neutrophils obtained from newborn foals and subsequently at 2-, 4-, and 8-weeks of age. Stimulation with virulent R. equi induced significantly (P<0.05) greater expression of IFNgamma, TNFalpha, IL-6, IL-8, IL-12p40, IL-12p35, and IL-23p19 mRNA relative to expression by unstimulated neutrophils, and there were significant effects of age on expression of IL-6, IL-8, IL-12p40 and IL-23p19. Neutrophil expression of IL-6 and IL-8 in newborn foals was significantly greater than expression at 2-, 4-, and 8-weeks of age. Expression of IL-12p40 by R. equi-stimulated neutrophils from newborn and 2-week-old foals did not differ from that of unstimulated neutrophils; however, expression of IL-12p40 by neutrophils from 4- and 8-week-old foals was significantly greater when stimulated by R. equi than without stimulation. These results demonstrate that foal neutrophils increase mRNA expression of many pro-inflammatory cytokines, including IFNgamma, in response to in vitro stimulation with R. equi, and that the magnitude of this expression with respect to IL-6, IL-8, IL-12p40 and IL-23p19 is influenced by age. The clinical importance of the age-related difference in R. equi-induced expression of IL-12p40 to susceptibility to R. equi pneumonia remains to be determined.
Publication Date: 2008-10-17 PubMed ID: 19026456DOI: 10.1016/j.vetimm.2008.10.004Google 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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This research article explores how the expression of certain proteins called cytokines, triggered by the presence of the bacteria Rhodococcus equi, changes in newborn foals as they age. The findings suggest that neutrophils, a type of white blood cell, trigger an inflammation response via these proteins, which varies depending on the age of the foal.

Research Context

  • The research is focused on the response by neutrophils, a type of white blood cells, in newborn foals to infection with Rhodococcus equi, a bacterium that often causes pneumonia in young foals.
  • While previous research has indicated that neutrophils are essential in counteracting R. equi infection, the mechanism through which neutrophils leverage their protective function has remained largely undefined.

Research Methodology

  • The researchers investigated the differences in the expression of cytokines, proteins responsible for cell communication in immune responses, by unstimulated and R. equi-stimulated neutrophils obtained from newborn foals and subsequently at 2-, 4-, and 8-weeks of age.
  • The expression levels of various types of cytokines (IFNgamma, TNFalpha, IL-6, IL-8, IL-12p40, IL-12p35, and IL-23p19) were measured both in the absence and presence of R. equi stimulation.

Key Findings

  • Owing to the stimulation by virulent R. equi, the expression of IFNgamma, TNFalpha, IL-6, IL-8, IL-12p40, IL-12p35, and IL-23p19 cytokines in neutrophils significantly increased compared to the expression level in absence of stimulation.
  • The study discovered significant age-related effects on the expression of IL-6, IL-8, IL-12p40, and IL-23p19.
  • Neutrophils in newborn foals expressed more IL-6 and IL-8 compared to those in 2-, 4- and 8-week-old foals.
  • Expression of cytokine IL-12p40 was similar in neutrophils from newborn and 2-week-old foals, regardless of stimulation. In contrast, the expression of IL-12p40 significantly increased in neutrophils from 4- and 8-week-old foals when stimulated by R. equi.

Implications

  • The research demonstrated that foal neutrophils increase the mRNA expression of many pro-inflammatory cytokines in response to in vitro stimulation with R. equi, and the intensity of this expression is influenced by the foal’s age.
  • The clinical significance of the age-related difference in R. equi-induced expression of IL-12p40 and its relation to susceptibility to R. equi pneumonia requires further investigation.

Cite This Article

APA
Nerren JR, Martens RJ, Payne S, Murrell J, Butler JL, Cohen ND. (2008). Age-related changes in cytokine expression by neutrophils of foals stimulated with virulent Rhodococcus equi in vitro. Vet Immunol Immunopathol, 127(3-4), 212-219. https://doi.org/10.1016/j.vetimm.2008.10.004

Publication

ISSN: 0165-2427
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 127
Issue: 3-4
Pages: 212-219

Researcher Affiliations

Nerren, Jessica R
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4475, United States.
Martens, Ronald J
    Payne, Susan
      Murrell, Jennifer
        Butler, Jamie L
          Cohen, Noah D

            MeSH Terms

            • Aging / immunology
            • Animals
            • Cells, Cultured
            • Cytokines / metabolism
            • Gene Expression Regulation / immunology
            • Horses / immunology
            • Neutrophils / metabolism
            • Neutrophils / microbiology
            • Rhodococcus equi / pathogenicity
            • Rhodococcus equi / physiology
            • Virulence

            Citations

            This article has been cited 6 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. 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
            3. 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
            4. 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
            5. Hildebrandt D, Venner M, Hart KA, Berghaus L. Plasma C-reactive protein and interleukin-6 concentrations in foals during health and respiratory disease. Equine Vet J 2026 Mar;58(2):372-379.
              doi: 10.1111/evj.70000pubmed: 40684375google scholar: lookup
            6. 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