In contrast to other species, α-Galactosylceramide (α-GalCer) is not an immunostimulatory NKT cell agonist in horses.
Abstract: α-GalCer is a potent immunomodulatory molecule that is presented to NKT cells via the CD1 antigen-presenting system. We hypothesized that when used as an adjuvant α-GalCer would induce protective immune responses against Rhodococcus equi, an important pathogen of young horses. Here we demonstrate that the equine CD1d molecule shares most features found in CD1d from other species and has a suitable lipid-binding groove for presenting glycolipids to NKT cells. However, equine CTL stimulated with α-GalCer failed to kill cells infected with R. equi, and α-GalCer did not increase killing by CTL co-stimulated with R. equi antigen. Likewise, α-GalCer did not induce the lymphoproliferation of equine PBMC or increase the proliferation of R. equi-stimulated cells. Intradermal injection of α-GalCer in horses did not increase the recruitment of lymphocytes or cytokine production. Furthermore, α-GalCer-loaded CD1d tetramers, which have been shown to be broadly cross-reactive, did not bind equine lymphocytes. Altogether, our results demonstrate that in contrast to previously described species, horses are unable to respond to α-GalCer. This raises questions about the capabilities and function of NKT cells and other lipid-specific T lymphocytes in horses.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication Date: 2014-11-10 PubMed ID: 25445911DOI: 10.1016/j.dci.2014.11.005Google 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 investigated the effect of a molecule, α-GalCer (alpha-galactosylceramide), on the immune response of horses, particularly in relation to a pathogen named Rhodococcus equi. Unlike in other species, results found that horses did not respond to α-GalCer, suggesting it cannot function as an immune-stimulator in this species.
Description of Investigation
- The study treated α-GalCer as a potential adjuvant, a substance that enhances the body’s immune response to an antigen, hypothesizing it would help protect against Rhodococcus equi, a bacterium causing a severe disease in foals.
- Researchers identified that the equine CD1d molecule—part of the machinery responsible for presenting α-GalCer to NKT immune cells—shares much in common with its counterparts in other species and has an appropriate lipid-binding groove for interacting with α-GalCer.
Discovery of Non-Responsiveness
- However, contrary to the hypothesis, the study found that equine cytotoxic T lymphocytes (CTL) stimulated with α-GalCer did not kill cells infected with R. equi.
- Even when these cells were co-stimulated with a R. equi antigen, α-GalCer still did not increase the effectiveness of the immune response.
- Similarly, α-GalCer did not induce lymphocyte proliferation (cell reproduction) in equine peripheral blood mononuclear cells (PBMCs)—another element of the immune system—nor did it boost the proliferation of cells already stimulated by R. equi.
- Administering α-GalCer through an intradermal injection (into the skin) also failed to improve the recruitment of immune cells or the production of cytokines, another aspect of a coordinated immune response.
- Making use of α-GalCer-loaded CD1d tetramers, a tool known to be cross-reactive across species, researchers found that these did not bind equine lymphocytes, again showing an immune response was not elicited.
Implications & Questions
- Considering these results, the study suggests that unlike in other species studied, horses are unable to respond to α-GalCer.
- This raises questions about the function and capabilities of Natural killer T (NKT) cells—immune cells known to interact with α-GalCer—and similar lipid-specific T lymphocytes in horses. Understanding this anomaly might help enhance the horse immune response to pathogens like R. equi in the future.
Cite This Article
APA
Dossa RG, Alperin DC, Garzon D, Mealey RH, Brown WC, Jervis PJ, Besra GS, Cox LR, Hines SA.
(2014).
In contrast to other species, α-Galactosylceramide (α-GalCer) is not an immunostimulatory NKT cell agonist in horses.
Dev Comp Immunol, 49(1), 49-58.
https://doi.org/10.1016/j.dci.2014.11.005 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Pathology, Washington State University, College of Veterinary Medicine, P.O. Box 647040, Pullman, WA 99164-7040, USA.
- Department of Veterinary Microbiology and Pathology, Washington State University, College of Veterinary Medicine, P.O. Box 647040, Pullman, WA 99164-7040, USA.
- Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
- Department of Veterinary Microbiology and Pathology, Washington State University, College of Veterinary Medicine, P.O. Box 647040, Pullman, WA 99164-7040, USA.
- Department of Veterinary Microbiology and Pathology, Washington State University, College of Veterinary Medicine, P.O. Box 647040, Pullman, WA 99164-7040, USA.
- School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
- School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
- School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
- Department of Veterinary Microbiology and Pathology, Washington State University, College of Veterinary Medicine, P.O. Box 647040, Pullman, WA 99164-7040, USA. Electronic address: shines@vetmed.wsu.edu.
MeSH Terms
- Adjuvants, Immunologic / chemistry
- Adjuvants, Immunologic / pharmacology
- Amino Acid Sequence
- Animals
- Antigens, CD1d / chemistry
- Antigens, CD1d / genetics
- Antigens, CD1d / immunology
- Cells, Cultured
- Galactosylceramides / chemistry
- Galactosylceramides / immunology
- Galactosylceramides / pharmacology
- Horse Diseases / immunology
- Horse Diseases / microbiology
- Horses / genetics
- Horses / immunology
- Horses / microbiology
- Host-Pathogen Interactions / immunology
- Humans
- Lymphocyte Activation / drug effects
- Lymphocyte Activation / immunology
- Mice
- Models, Molecular
- Molecular Sequence Data
- Molecular Structure
- Natural Killer T-Cells / immunology
- Natural Killer T-Cells / metabolism
- Phylogeny
- Protein Structure, Tertiary
- Rhodococcus equi / immunology
- Rhodococcus equi / physiology
- Sequence Homology, Amino Acid
Grant Funding
- G1001750 / Medical Research Council
Citations
This article has been cited 2 times.- Sage SE, Nicholson P, Peters LM, Leeb T, Jagannathan V, Gerber V. Single-cell gene expression analysis of cryopreserved equine bronchoalveolar cells. Front Immunol 2022;13:929922.
- Driver JP, de Carvalho Madrid DM, Gu W, Artiaga BL, Richt JA. Modulation of Immune Responses to Influenza A Virus Vaccines by Natural Killer T Cells. Front Immunol 2020;11:2172.
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