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



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



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.



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.
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Thais F C
TF
Fraga-Silva
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Luiza A N
LA
Mimura
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Sofia F G
SF
Zorzella-Pezavento
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Larissa L W
LL
Ishikawa
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Thais G D
TG
França
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Rodolfo
R
Thomé
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
Liana
L
Verinaud
Department of Biological Sciences, School of Sciences, Univ. Estadual Paulista (UNESP), Bauru, São Paulo, Brazil.
Maria S P
MS
Arruda
Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil. sartori@ibb.unesp.br.
Alexandrina
A
Sartori
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002176:Candida albicans / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000473:pathology; D002762:Cholecalciferol / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D014815:Vitamins / Q000627:therapeutic use*
D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D063308:Myelin-Oligodendrocyte Glycoprotein; D014815:Vitamins; D002762:Cholecalciferol
Active vitamin D; Disseminated candidiasis; Multiple sclerosis; Myelin oligodendrocyte glycoprotein; Tolerogenic vaccination