title: 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.
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, College of Veterinary Medicine, P.O. Box 647040, Pullman, WA 99164-7040, USA.
authors.forename: Robson G
authors.initials: RG
authors.lastname: Dossa
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, College of Veterinary Medicine, P.O. Box 647040, Pullman, WA 99164-7040, USA.
authors.forename: Debra C
authors.initials: DC
authors.lastname: Alperin
authors.affiliation: Unilever Centre for Molecular Science Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Garzon
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, College of Veterinary Medicine, P.O. Box 647040, Pullman, WA 99164-7040, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mealey
authors.affiliation: Department of Veterinary Microbiology and Pathology, Washington State University, College of Veterinary Medicine, P.O. Box 647040, Pullman, WA 99164-7040, USA.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Brown
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Jervis
authors.affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.affiliation: School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Liam R
authors.initials: LR
authors.lastname: Cox
authors.affiliation: 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.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Hines
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D055610:Antigens, CD1d / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005699:Galactosylceramides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D006734:Horse Diseases / Q000276:immunology / Q000382:microbiology; D006736:Horses / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D016929:Rhodococcus equi / Q000276:immunology / Q000502:physiology; D017386:Sequence Homology, Amino Acid
chemical_list: D000276:Adjuvants, Immunologic; D055610:Antigens, CD1d; D005699:Galactosylceramides; C493154:alpha-galactosylceramide
keywords: CD1d; Horse; NKT; Rhodococcus equi; α-Galactosylceramide