Effect of hay dust extract and cyathostomin antigen stimulation on cytokine expression by PBMC in horses with recurrent airway obstruction.
Abstract: Equine recurrent airway obstruction (RAO) is an inflammatory, obstructive airway disease induced by exposure of susceptible horses to inhaled organic dust particles. The immunological process underlying RAO is still unclear. Previous studies have shown that RAO is linked to the Interleukin-4 receptor (IL-4R) gene in one Warmblood family (F1), but not in another (F2). It has also been shown that in F1, but not in F2, RAO is associated with resistance against parasites, suggesting that this association may have an immuno-genetic basis. Therefore, we hypothesized that the T helper (h)1/Th2/regulatory (Treg) cytokine profiles of RAO-associated antigen- and parasite-antigen-stimulated peripheral blood mononuclear cells (PBMC) differ between RAO-affected and healthy horses depending on their genetic background. In our study, PBMC from 17 RAO-affected and 14 healthy control horses of F1 and F2 were stimulated for 24h with antigens relevant to RAO [hay dust extract (HDE), Aspergillus fumigatus extract (AFE) and lipopolysaccharids (LPS)]; cyathostomin extract (CE) and recombinant cyathostomin antigen (RCA) or with concanavalin A (ConA). Total mRNA levels of IL-4, IL-4R, IL-13, interferon (INF)-γ and IL-10 were examined by qRT-PCR. Stimulation with either HDE or RCA resulted in significant differences in IL-4R mRNA levels between RAO-affected and control horses in F1, but not in F2. For IL-10 mRNA expression, a significant difference between RAO-affected and control horses in F1 but not in F2 was observed only following stimulation with HDE. In contrast to HDE, stimulation with CE resulted in a significant difference of IL-10 mRNA expression level between RAO-affected horses of F2 and healthy horses of F1. No significant differences were detected upon stimulation with any of the other challenge agents. These findings indicate that the immunological response, specifically IL-4R expression, in response to hay dust and cyathostomin antigens, differs between RAO-affected and healthy horses depending on their genetic background. This study shows that analysis of PBMC reveals systemic changes associated with RAO and helps to elucidate immunological pathways involved in this disease.
Copyright © 2013 Elsevier B.V. All rights reserved.
Publication Date: 2013-08-05 PubMed ID: 23972861DOI: 10.1016/j.vetimm.2013.07.005Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Antigen
- Clinical Study
- Cyathostomins
- Cytokines
- Diagnosis
- Disease Diagnosis
- Disease Etiology
- Equine Diseases
- Equine Health
- Genetics
- Hay
- Horses
- Immune Response
- Immunology
- In Vivo
- Infection
- Inflammation
- Interleukins
- Mononuclear Cells
- Parasites
- Pathogenesis
- Recurrent Airway Obstruction
- Respiratory Disease
- Veterinary Medicine
- Veterinary Research
- Warmblood Horses
Summary
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The research article presents a study exploring the immunological response, specifically involving IL-4R expression, to hay dust and cyathostomin antigens in horses suffering from equine recurrent airway obstruction (RAO) as compared to healthy horses. The results showcase varying responses based on genetic background, indicating potential immuno-genetic aspects of RAO.
Objective and Hypothesis
- The objective of the research was to explore the immunological process underlying equine recurrent airway obstruction (RAO), an inflammatory airway disease in horses that is induced by exposure to inhaled organic dust particles.
- The researchers hypothesized that T helper (h)1/Th2/regulatory (Treg) cytokine profiles would differ between RAO-afflicted and healthy horses on exposure to RAO-associated antigens and parasite antigens, and that this difference would be dependent on the horse’s genetic background.
Methodology
- The researchers obtained peripheral blood mononuclear cells (PBMC) from 17 RAO-affected and 14 healthy horses.
- These PBMC were stimulated for 24 hours with antigens relevant to RAO — hay dust extract (HDE), Aspergillus fumigatus extract (AFE), lipopolysaccharids (LPS), cyathostomin extract (CE), and recombinant cyathostomin antigen (RCA) — as well as concanavalin A (ConA).
- Using qRT-PCR, the researchers examined the total mRNA levels of various immunological markers: IL-4, IL-4R, IL-13, interferon (INF)-γ, and IL-10.
Findings
- RAO-affected and control horses from Warmblood family F1 showed significant differences in IL-4R mRNA levels post stimulation with HDE or RCA. These differences, however, did not emerge in the horses from Warmblood family F2.
- On stimulation with HDE, IL-10 mRNA expression varied significantly between RAO-affected and control horses in F1, but not F2.
- When stimulated with CE, the IL-10 mRNA expression levels were significantly different between RAO-affected horses of F2 and healthy horses of F1.
- No significant differences were identified when the researchers stimulated the PBMC with any of the other antigens they tested.
Conclusions
- The study demonstrated variations in immunological response, particularly of IL-4R expression, to hay dust and cyathostomin antigens between RAO-affected and healthy horses, suggesting a genetic influencing aspect to immunological responses in RAO.
- The utilization of PBMC in tests revealed systemic changes linked to RAO and provided insights into the specific pathways related to this disease on an immunological level.
Cite This Article
APA
Lanz S, Gerber V, Marti E, Rettmer H, Klukowska-Rötzler J, Gottstein B, Matthews JB, Pirie S, Hamza E.
(2013).
Effect of hay dust extract and cyathostomin antigen stimulation on cytokine expression by PBMC in horses with recurrent airway obstruction.
Vet Immunol Immunopathol, 155(4), 229-237.
https://doi.org/10.1016/j.vetimm.2013.07.005 Publication
Researcher Affiliations
- Swiss Institute of Equine Medicine, University of Bern and ALP-Haras, Switzerland. Electronic address: Simone.Lanz@vetsuisse.unibe.ch.
MeSH Terms
- Airway Obstruction / genetics
- Airway Obstruction / immunology
- Airway Obstruction / veterinary
- Animals
- Dust / immunology
- Female
- Horse Diseases / genetics
- Horse Diseases / immunology
- Horses
- Interferon-gamma / genetics
- Interferon-gamma / immunology
- Interleukin-10 / genetics
- Interleukin-10 / immunology
- Interleukin-13 / genetics
- Interleukin-13 / immunology
- Interleukin-4 / genetics
- Interleukin-4 / immunology
- Leukocytes, Mononuclear
- Male
- Nematoda / immunology
- RNA, Messenger / chemistry
- RNA, Messenger / genetics
- Receptors, Interleukin-4 / genetics
- Receptors, Interleukin-4 / immunology
- Reverse Transcriptase Polymerase Chain Reaction / veterinary
Citations
This article has been cited 7 times.- Raudsepp T, Finno CJ, Bellone RR, Petersen JL. Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post-genome era.. Anim Genet 2019 Dec;50(6):569-597.
- Mason VC, Schaefer RJ, McCue ME, Leeb T, Gerber V. eQTL discovery and their association with severe equine asthma in European Warmblood horses.. BMC Genomics 2018 Aug 2;19(1):581.
- Pacholewska A, Kraft MF, Gerber V, Jagannathan V. Differential Expression of Serum MicroRNAs Supports CD4⁺ T Cell Differentiation into Th2/Th17 Cells in Severe Equine Asthma.. Genes (Basel) 2017 Dec 12;8(12).
- Pacholewska A, Marti E, Leeb T, Jagannathan V, Gerber V. LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells.. BMC Genomics 2017 Jan 5;18(1):34.
- Pacholewska A, Mach N, Mata X, Vaiman A, Schibler L, Barrey E, Gerber V. Novel equine tissue miRNAs and breed-related miRNA expressed in serum.. BMC Genomics 2016 Oct 26;17(1):831.
- Pacholewska A, Jagannathan V, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Leeb T, Gerber V. Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.. PLoS One 2015;10(8):e0136103.
- Pacholewska A, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Gerber V, Leeb T, Jagannathan V. The transcriptome of equine peripheral blood mononuclear cells.. PLoS One 2015;10(3):e0122011.
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