Allergen-Specific Cytokine Polarization Protects Shetland Ponies against Culicoides obsoletus-Induced Insect Bite Hypersensitivity.
Abstract: The immunological mechanisms explaining development of an allergy in some individuals and not in others remain incompletely understood. Insect bite hypersensitivity (IBH) is a common, seasonal, IgE-mediated, pruritic skin disorder that affects considerable proportions of horses of different breeds, which is caused by bites of the insect Culicoides obsoletus (C. obsoletus). We investigated the allergen-specific immune status of individual horses that had either been diagnosed to be healthy or to suffer of IBH. Following intradermal allergen injection, skin biopsies were taken of IBH-affected and healthy ponies and cytokine expression was determined by RT-PCR. In addition, allergen-specific antibody titers were measured and cytokine expression of in vitro stimulated, allergen-specific CD4 T-cells was determined. 24 hrs after allergen injection, a significant increase in mRNA expression of the type-2 cytokine IL-4 was observed in the skin of IBH-affected Shetland ponies. In the skin of healthy ponies, however, an increase in IFNγ mRNA expression was found. Analysis of allergen-specific antibody titers revealed that all animals produced allergen-specific antibodies, and allergen-specific stimulation of CD4 T-cells revealed a significant higher percentage of IFNγ-expressing CD4 T-cells in healthy ponies compared to IBH-affected ponies. These data indicate that horses not affected by IBH, in contrast to the so far established dogma, are not immunologically ignorant but have a Th1-skewed allergen-specific immune response that appears to protect against IBH-associated symptoms. To our knowledge this is the first demonstration of a natural situation, in which an allergen-specific immune skewing is protective in an allergic disorder.
Publication Date: 2015-04-22 PubMed ID: 25901733PubMed Central: PMC4406554DOI: 10.1371/journal.pone.0122090Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates why only some individuals develop allergens through a study of Insect Bite Hypersensitivity (IBH) in Shetland ponies. The study found that horses not affected by IBH are not immunologically ignorant, but have a Th1-skewed allergen-specific immune response that protects against IBH.
Research Objective
- The research aimed to understand the immunological mechanisms that lead to the development of i/> allergies in some individuals and not in others. In particular, it sought to explain the common occurrence of Insect Bite Hypersensitivity (IBH) in horses, caused by bites from the insect Culicoides obsoletus (C. obsoletus).
Research Methodology
- The researchers investigated the allergen-specific immune status of individual horses that had either been diagnosed as healthy or suffering from IBH.
- After intradermal allergen injection, skin biopsies were taken from both IBH-affected and healthy ponies and analyzed through RT-PCR to determine cytokine expression.
- Allergen-specific antibody titers were measured, and the cytokine expression of in vitro stimulated, allergen-specific CD4 T-cells was determined.
Research Findings
- 24 hours after allergen injection, there was a significant increase in the mRNA expression of the type-2 cytokine IL-4 in the skin of the IBH-affected Shetland ponies.
- In contrast, the skin of healthy ponies indicated an increase in IFNγ mRNA expression.
- All the animals produced allergen-specific antibodies, but the allergen-specific stimulation of CD4 T-cells revealed a significantly higher percentage of IFNγ-expressing CD4 T-cells in healthy ponies compared to those with IBH.
Implications of the Research
- This study suggests that horses not affected by IBH are not immunologically ignorant, but display a Th1-skewed allergen-specific immune response that protects them against the symptoms of IBH.
- This is the first demonstration of a natural situation where an allergen-specific immune response is protective against an allergic disorder.
Cite This Article
APA
Meulenbroeks C, van der Lugt JJ, van der Meide NM, Willemse T, Rutten VP, Zaiss DM.
(2015).
Allergen-Specific Cytokine Polarization Protects Shetland Ponies against Culicoides obsoletus-Induced Insect Bite Hypersensitivity.
PLoS One, 10(4), e0122090.
https://doi.org/10.1371/journal.pone.0122090 Publication
Researcher Affiliations
- Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
- IDEXX Laboratories, Hoofddorp, The Netherlands.
- Department of Cell Biology & Immunology, Wageningen University, Wageningen, The Netherlands.
- Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands; Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
- Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands; Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Pretoria, Onderstepoort, South Africa.
- Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands; Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, EH9 3JT, United Kingdom.
MeSH Terms
- Allergens / administration & dosage
- Allergens / immunology
- Animals
- Antibodies / blood
- CD4-Positive T-Lymphocytes / immunology
- Ceratopogonidae / classification
- Ceratopogonidae / immunology
- Horses
- Humans
- Hypersensitivity / immunology
- Immune Tolerance
- Insect Bites and Stings
- Interferon-gamma / immunology
Grant Funding
- 095831 / Wellcome Trust
Conflict of Interest Statement
The authors have the following interests: Co-author Jaco J. van der Lugt is employed by IDEXX Laboratories. This study was funded in part by ALK-Abelló and Artu Biologicals. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.
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Citations
This article has been cited 2 times.- Cvitas I, Oberhaensli S, Leeb T, Marti E. Equine keratinocytes in the pathogenesis of insect bite hypersensitivity: Just another brick in the wall?. PLoS One 2022;17(8):e0266263.
- Birras J, White SJ, Jonsdottir S, Novotny EN, Ziegler A, Wilson AD, Frey R, Torsteinsdottir S, Alcocer M, Marti E. First clinical expression of equine insect bite hypersensitivity is associated with co-sensitization to multiple Culicoides allergens.. PLoS One 2021;16(11):e0257819.
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