4.7 Article

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

Journal

CNS NEUROSCIENCE & THERAPEUTICS
Volume 22, Issue 10, Pages 807-816

Publisher

WILEY-BLACKWELL
DOI: 10.1111/cns.12572

Keywords

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

Funding

  1. Sao Paulo Research Foundation (FAPESP) [2012/12540-7]
  2. FAPESP [2013/ 14353-2]

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AimsMultiple 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. MethodsEAE was induced in C57BL/6 female mice previously vaccinated with MOG+VitD and then infected 3 days before encephalomyelitis induction. ResultsVaccination 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. ConclusionTogether, 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.

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