title: Murine pattern recognition receptor dectin-1 is essential in the development of experimental autoimmune uveoretinitis.
abstract: Mycobacteria in complete Freund's adjuvant (CFA) are an essential component of immunization protocols in a number of autoimmune disease animal models including experimental autoimmune encephalomyelitis and uveoretinitis (EAE and EAU, respectively). We determined the role in EAU of two C-type lectin receptors on myeloid cells that recognize and respond to mycobacteria. Using receptor-specific antibodies and knockout mice, we demonstrated for the first time that the macrophage mannose receptor delays disease development but does not affect severity. In contrast, dectin-1 is critically involved in the development of CFA-mediated EAU. Disease severity is reduced in dectin-1 knockout mice and antibody blockade of dectin-1 during the induction, but not the effector phase, prevents EAU development. Significantly, similar blockade of dectin-1 in vivo has no effect in non-CFA-mediated, spontaneously induced or adoptive transfer models of EAU. Thus dectin-1 plays a critical role in the ability of complete Freund's adjuvant to induce EAU in mice.
authors.affiliation: Section of Immunology and Infection, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland, United Kingdom. Electronic address: sandra.stoppelkamp@uni-tuebingen.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Stoppelkamp
authors.affiliation: Section of Immunology and Infection, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland, United Kingdom. Electronic address: delyth.reid@abdn.ac.uk.
authors.forename: Delyth M
authors.initials: DM
authors.lastname: Reid
authors.affiliation: Section of Immunology and Infection, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland, United Kingdom. Electronic address: jooce@scientist.com.
authors.forename: Joyce
authors.initials: J
authors.lastname: Yeoh
authors.affiliation: Section of Immunology and Infection, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland, United Kingdom. Electronic address: j.a.taylor@abdn.ac.uk.
authors.forename: Julie
authors.initials: J
authors.lastname: Taylor
authors.affiliation: Section of Immunology and Infection, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland, United Kingdom. Electronic address: e.j.mckenzie@dundee.ac.uk.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: McKenzie
authors.affiliation: Section of Immunology and Infection, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland, United Kingdom. Electronic address: gordon.brown@abdn.ac.uk.
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, England, United Kingdom. Electronic address: siamon.gordon@path.ox.ac.uk.
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.affiliation: Section of Immunology and Infection, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland, United Kingdom; Immunology and Virology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA, Australia; Centre for Experimental Immunology, Lions Eye Institute, Nedlands, WA, Australia. Electronic address: j.forrester@abdn.ac.uk.
authors.forename: John V
authors.initials: JV
authors.lastname: Forrester
authors.affiliation: Section of Immunology and Infection, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland, United Kingdom. Electronic address: simon.y.c.wong@abdn.ac.uk.
authors.forename: Simon Y C
authors.initials: SY
authors.lastname: Wong
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000276:immunology; D006801:Humans; D007114:Immunization; D018836:Inflammation Mediators / Q000378:metabolism; D037181:Lectins, C-Type / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051192:Receptors, Pattern Recognition / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012173:Retinitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014605:Uveitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000099181:Dectin-1
chemical_list: D019138:Antibodies, Blocking; D018925:Chemokines; D005620:Freund's Adjuvant; D018836:Inflammation Mediators; D037181:Lectins, C-Type; D051192:Receptors, Pattern Recognition; D012177:Retinol-Binding Proteins; D000099181:Dectin-1
keywords: Adjuvant; Dectin-1; Experimental autoimmune uveitis; Macrophage mannose receptor; Mycobacteria; Pattern recognition receptor