Tolerogenic Vaccination with MOG/VitD Overcomes Aggravating Effect of C. albicans in Experimental Encephalomyelitis

CNS Neurosci Ther. 2016 Oct;22(10):807-16. doi: 10.1111/cns.12572. Epub 2016 Jun 19.

Abstract

Aims: Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system (CNS). We described that Candida albicans (Ca) aggravates experimental autoimmune encephalomyelitis (EAE) that is a model to study MS. We also observed that vaccination with a myelin peptide (MOG) in the presence of vitamin D (VitD) protected mice against EAE. In this work, we investigated whether Ca infection interferes with the efficacy of this vaccine.

Methods: EAE was induced in C57BL/6 female mice previously vaccinated with MOG+VitD and then infected 3 days before encephalomyelitis induction.

Results: Vaccination was able to control EAE development in infected mice. These animals gained weight, and only a few progressed to very low clinical scores. Protection was confirmed by a lower inflammatory infiltration in the CNS and was also associated with a reduced production of encephalitogenic cytokines by spleen and CNS cell cultures. The elevated percentage of CD25(+) FoxP3(+) cells suggests that regulatory T cells are involved in the protection. Adoptive transfer of splenocytes from mice vaccinated with MOG+VitD supports the view that protection is mediated by immunoregulatory cells.

Conclusion: Together, these experiments provide evidence demonstrating that EAE can be prevented by the inverse vaccination with MOG+VitD even in the presence of a disease-aggravating infectious agent.

Keywords: Active vitamin D; Disseminated candidiasis; Multiple sclerosis; Myelin oligodendrocyte glycoprotein; Tolerogenic vaccination.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Candida albicans / pathogenicity
  • Candidiasis / immunology
  • Candidiasis / physiopathology
  • Candidiasis / therapy*
  • Cells, Cultured
  • Central Nervous System / pathology
  • Cholecalciferol / therapeutic use*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Encephalomyelitis, Autoimmune, Experimental / therapy
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Lymph Nodes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Vitamins / therapeutic use*

Substances

  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Myelin-Oligodendrocyte Glycoprotein
  • Vitamins
  • Cholecalciferol

Associated data

  • GENBANK/EF591020