Murine pattern recognition receptor dectin-1 is essential in the development of experimental autoimmune uveoretinitis

Mol Immunol. 2015 Oct;67(2 Pt B):398-406. doi: 10.1016/j.molimm.2015.07.002. Epub 2015 Jul 26.

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.

Keywords: Adjuvant; Dectin-1; Experimental autoimmune uveitis; Macrophage mannose receptor; Mycobacteria; Pattern recognition receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / pharmacology
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism*
  • Autoimmune Diseases / pathology
  • Chemokines / metabolism
  • Disease Models, Animal
  • Freund's Adjuvant / immunology
  • Humans
  • Immunization
  • Inflammation Mediators / metabolism
  • Lectins, C-Type / deficiency
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism*
  • Lymph Nodes / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Pattern Recognition / deficiency
  • Receptors, Pattern Recognition / immunology
  • Receptors, Pattern Recognition / metabolism*
  • Retina / drug effects
  • Retina / metabolism
  • Retina / pathology
  • Retinitis / immunology
  • Retinitis / metabolism*
  • Retinitis / pathology
  • Retinol-Binding Proteins / metabolism
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology
  • Time Factors
  • Uveitis / immunology
  • Uveitis / metabolism*
  • Uveitis / pathology

Substances

  • Antibodies, Blocking
  • Chemokines
  • Inflammation Mediators
  • Lectins, C-Type
  • Receptors, Pattern Recognition
  • Retinol-Binding Proteins
  • dectin 1
  • Freund's Adjuvant