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| Author(s): |
Thais Fernanda de Campos Fraga Silva
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Botucatu. 2016-04-15. |
| Institution: | Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu |
| Defense date: | 2016-02-25 |
| Advisor: | Alexandrina Sartori |
| Abstract | |
Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS). Data from patients and experimental models suggest that fungal infection and fungalderived antigens could contribute to the immunopathogenesis of this pathology. The main objective of this research was to investigate the effect of C. albicans and fungal derivatives on experimental autoimmune encephalomyelitis (EAE) that is a widely employed animal model to study MS. Initially, C57BL/6 mice were infected with C. albicans and three days later they were submitted to EAE induction. Infected animals developed a more severe disease associated with fungus spread to the CNS and increased production of encephalitogenic cytokines as TNF-α, IL-6, IL-17 and IFN-γ by cells from the spleen and the CNS. To test the effect of fungal derivatives mice were submitted to EAE induction and then injected with three doses of gliotoxin or dead yeasts of C. albicans. Gliotoxin inoculation resulted in clinical disease aggravation, higher local inflammatory infiltration and higher production of TNF-α by the CNS. Dead C. albicans inoculation determined a less severe disease associated with a lower production of encephalitogenic cytokines and a lower degree of apoptosis by CNS eluted cells. Lastly we demonstrated that C. albicans infection did not disrupt the prophylactic efficacy of MOG+VitD tolerogenic vaccination. Even in infected mice this vaccine decreased clinical signs, downmodulated the production of encephalitogenic cytokines and also increased the percentage of regulatory T cells. All together these results indicate that C. albicans infection and gliotoxin inoculation aggravate EAE development whereas dead C. albicans inoculation protected the animals. (AU) | |
| FAPESP's process: | 13/14353-2 - Effect of Candida albicans infection on experimental Autoimmune Encephalitis Development |
| Grantee: | Thais Fernanda de Campos Fraga da Silva |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |