Tolerogenic Vaccination with MOG/VitD Overcomes Aggravating Effect of C. albicans in Experimental Encephalomyelitis
Thais F C Fraga-Silva1, Luiza A N Mimura1, Sofia F G Zorzella-Pezavento1
1Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
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.
Insights
This study shows that vaccination with myelin peptide and vitamin D effectively prevents experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, even when mice are infected with Candida albicans.
Area of Science:
- Neuroimmunology
- Infectious Disease Immunology
Background:
- Multiple sclerosis (MS) is a CNS demyelinating disorder.
- Candida albicans (Ca) infection exacerbates experimental autoimmune encephalomyelitis (EAE), an MS model.
- Vaccination with myelin peptide (MOG) and vitamin D (VitD) previously showed protective effects against EAE.
Purpose of the Study:
- To investigate if Ca infection impacts the efficacy of MOG+VitD vaccination against EAE.
- To determine the immunoregulatory mechanisms underlying protection.
Main Methods:
- EAE was induced in C57BL/6 female mice vaccinated with MOG+VitD.
- Mice were infected with Ca three days before EAE induction.
- Immune cell analysis and cytokine production were assessed.
Main Results:
- MOG+VitD vaccination controlled EAE in Ca-infected mice, with minimal clinical scores and weight loss.
- Reduced CNS inflammation and lower production of encephalitogenic cytokines were observed.
- Increased CD25(+) FoxP3(+) regulatory T cells and successful adoptive transfer of splenocytes indicated immune regulation.
Conclusions:
- MOG+VitD vaccination is effective in preventing EAE, even with concurrent Ca infection.
- The protective effect is mediated by immunoregulatory cells, likely involving regulatory T cells.
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